bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal plasma levels of cytokines in normal and preeclamptic pregnancies and their relationship with diastolic blood pressure and fibronectin levels
Authors: Madazli Riza , Aydin Seval , Uludag Seyfettin , Vildan Ocak. , Tolun Necati
Published: August 2003

Background.  To determine the plasma concentrations of placental growth factor (PLGF), vascular endothelial growth factor (VEGF), transforming growth factor‐β1 (TGF‐β1), soluble tumor necrosis factor α receptor (sTNFp55), interleukin‐2 receptor (IL‐2R), and interleukins 6 and 10 (IL‐6, IL‐10) in normotensive and preeclamptic women, and to evaluate the correlations between these cytokines and the diastolic blood pressure and fibronectin levels.

Methods.  A prospective case–control study. Thirty‐five women with preeclampsia were compared with 34 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained and plasma levels of PLGF, VEGF, TGF‐β1, sTNFp55, IL‐2R, IL‐6 and IL‐10 were measured by an enzyme‐linked immunoassay and fibronectin by a radial immundiffusion technic.

Results.  In preeclampsia PLGF and VEGF levels were significantly lower, and TGF‐β1, sTNFp55, IL‐2R, IL‐6 and IL‐10 levels were significantly higher than in normotensive pregnancy (p < 0.001). The plasma levels of PLGF and VEGF significantly decreased, whereas TGF‐β1, sTNFp55, IL‐2R, IL‐6 and IL‐10 levels significantly increased with the increments in diastolic blood pressure and fibronectin levels (p < 0.001).

Conclusions.  Altered concentrations of various cytokines might explain the shallow placentation and endothelial cell dysfunction described in preeclampsia. The clinical severity of preeclampsia seems to correlate with the severity of the cytokine abnormalities.
Undiagnosed term breech: Impact on mode of delivery and neonatal outcome
Authors: Usta Ihab M. , Nassar Anwar H. , Khabbaz Antoun Y. , Abu Musa Antoine A.
Published: August 2003

Background.  The purpose of this study was to compare delivery mode and neonatal outcome in breech pregnancies diagnosed antepartum (Dx group) with those diagnosed on admission for delivery or intrapartum (No‐Dx group).

Methods.  During an 11‐year period, breech pregnancies ≥34 weeks' gestation with a live nonanomalous fetus were reviewed. The Dx group was matched for gestational age, parity, and maternal age to the No‐Dx group (n = 256) and compared using the χ2‐test, the Mc‐Nemar test, and the Wilcoxon rank test. A p‐value of < 0.05 was considered significant.

Results.  Breech type and birthweights were similar in the two groups. In the No‐Dx group, 19.5% did not receive prenatal care. More patients in the No‐Dx group were admitted with cervical dilation > 4 cm (39.4% vs. 27.0%, p = 0.004), whereas 17.1% of patients in the Dx group were admitted for elective cesarean delivery at term. There was a higher cesarean delivery rate in the Dx group (64.1% vs. 50.8%, p = 0.003), specifically for arrest disorders (15.2% vs. 6.9%, p = 0.008). The neonatal outcome in the two groups was similar regarding Apgar scores, intensive care nursery admission, need for mechanical ventilation, neonatal death, and length of nursery stay.

Conclusions.  Antepartum diagnosis of breech presentation decreases the threshold for cesarean delivery. Failure to diagnose breech antepartum does not compromise neonatal outcome.
Pitfalls in diagnosis of interstitial pregnancy
Authors: Chan Louis Yik‐Si , Fok Wing Yee , Yuen Pong Mo
Published: August 2003

Background.  To determine the incidence and reasons for misdiagnosis in interstitial ectopic pregnancy.

Methods.  We conducted a retrospective study from 1990 to 2001. Women with interstitial pregnancy were identified and their case records retrieved and reviewed. Reasons for delay in diagnosis and associated morbidity were recorded.

Results.  Thirty‐six women were diagnosed as having interstitial pregnancy during the study period. Initial diagnosis was incorrect in 15 cases (41.7%). In 14 cases, the interstitial pregnancies were mistaken as intrauterine pregnancy. These misdiagnoses resulted in six inappropriate surgical procedures (evacuation of uterus) being performed and led to rupture of interstitial pregnancy in eight women. In two women, the interstitial pregnancy was mistaken as normal intrauterine pregnancy while the uterus itself was thought to be a cervical fibroid. In both cases, the interstitial pregnancies ruptured at 18–20 weeks of gestation.

Conclusion.  Despite advances in sonographic skills and equipment and the availability of β‐human chorionic gonadotropin (hCG) monitoring, misdiagnosis of interstitial pregnancy still occurs frequently. Clinicians should be aware of the limitations of various investigations and maintain a high index of suspicion.
A randomized trial comparing changes in psychological well‐being and sexuality after laparoscopic and abdominal hysterectomy
Authors: Ellström Marie A. , Åström Monica , Möller Anders , Olsson Jan‐Henrik , Hahlin Mats
Published: August 2003

Background.  To evaluate changes in psychological well‐being and sexuality 1 year after laparoscopic and abdominal hysterectomy.

Material and methods.  Seventy‐four women scheduled for abdominal hysterectomy due to benign disorders and assessed as not suitable for vaginal hysterectomy were randomized to abdominal hysterectomy (n = 38) or laparoscopic hysterectomy (n = 36). The Psychological General Well‐Being (PGWB) Index was used to evaluate changes in psychological well‐being and the McCoy scale was used to evaluate changes in sexuality. The differences in outcome before and 1 year after the hysterectomy were calculated for each individual and the changes were compared within and between the two patient groups.

Results.  There were no significant differences between the two patient groups with respect to changes in psychological well‐being and sexuality 1 year after surgery.

Conclusions.  This study implies that psychological well‐being and sexuality after hysterectomy are not influenced by surgical technique.
Effect of antenatal corticosteroid administration on Doppler flow velocity parameters in pregnancies with absent or reverse end‐diastolic flow in the umbilical artery
Authors: Müller Thomas , Nanan Ralph , Dietl Johannes
Published: August 2003

Objective.  Evaluation of alterations of Doppler flow velocity waveforms after antenatal corticosteroid therapy.

Methods.  Pulsatility index of the umbilical artery, middle cerebral artery and ductus venosus waveforms was measured in high‐risk pregnancies complicated by umbilical AREDV directly prior to and within 24 or 48 hours after application of the first dose of a steroid treatment course.

Results.  Return of a positive end‐diastolic flow after umbilical AREDV or conversion of REDV into zero‐flow was detected in 9 of 20 (45%) pregnancies after steroid application. Neither in the group which showed altered umbilical end‐diastolic flow nor in the total of patients investigated was there any significant change in the PI of the umbilical artery or the ductus venosus waveforms. In contrast, there was an overall drop of pulsatility in the middle cerebral artery.

Conclusions.  Antenatal corticosteroid administration could increase cerebral perfusion but has no influence on umbilical and venous blood flow.
Multimodal intervention raises smoking cessation rate during pregnancy
Authors: Hegaard Hanne K. , KjÆrgaard Hanne , MØller Lars F. , Wachmann Henrik , Ottesen Bent
Published: August 2003

Background.  The aim was to study the effect of a multimodal smoking cessation intervention regimen on a number of pregnant smokers.

Methods.  A prospective intervention study was designed where participants were allocated to intervention or control based on their birth date. The study included 647 pregnant smokers. The intervention group (n = 327) received initial individual smoking cessation counseling supplemented by an invitation to join, individually or in a group, a smoking cessation program with nicotine replacement therapy as a voluntary option. Intervention was designed as an integral part of the midwives' prenatal care. All pregnant smokers in the usual care group (n = 320) received standard counseling from a midwife. Outcome was self‐reported smoking cessation in the 37th week of pregnancy and the reported cessation was validated by cotinine saliva concentration.

Results.  Self‐reported cessation rates during pregnancy were significantly higher in the intervention group (14%) than in the group receiving usual care (5.0%) (p < 0.0001) (Fisher's exact test). Cotinine‐validated cessation rates during pregnancy were significantly higher among the former (7%) than the latter (2%) (p = 0.003). The adjusted odds ratio (OR) for smoking cessation was 4.20 (95% CI 2.13–8.03). Logistic regression analysis showed a significant positive association of smoking cessation with low caffeine consumption in pregnancy, many years in school, no exposure to passive smoking outside the home, and previous attempts to stop smoking.

Conclusions.  A multimodal intervention regimen with initial individual counseling supplemented by an invitation to join a smoking cessation program with nicotine replacement therapy as a voluntary option markedly increased cessation rates during pregnancy.
Obstetric and neonatal risk of pregnancies after assisted reproductive technology: a matched control study
Authors: Kozinszky Zoltán , Zádori János , Orvos Hajnalka , Katona Márta , Pál Attila , Kovács László
Published: August 2003

Background.  The aim of the study was to evaluate the obstetric and neonatal outcome of pregnancies after assisted reproduction technology (ART) in comparison with matched controls from spontaneous pregnancies.

Methods.  A total of 12 920 deliveries at the Department of Obstetrics and Gynecology, University of Szeged, from 1 January 1995 to 31 December 2001 were subjected to retrospective analysis. Two hundred and eighty‐four singleton, 75 twin and 17 triplet pregnancies after ovulation induction (n = 114; 30.3%), intrauterine insemination (n = 33; 8.8%) and in vitro fertilization (n = 229; 60.9%) were evaluated. The pregnancy outcome of the singleton and twin pregnancies was compared with that for controls matched with regard to age, gravidity and parity and previous obstetric outcome after spontaneous pregnancies.

Results.  Twenty‐four percent of the assisted reproductive pregnancies were multiple pregnancies. The incidences of singleton intrauterine growth retardation (IUGR) and preterm birth were reasonably similar to those among the controls (IUGR: 6.3% vs. 4.2%; preterm births: 13.0% vs. 9.9%, for the cases and the controls, respectively). As compared with the controls, there was an increased incidence of cesarean section among the singleton (41.2% vs. 34.5%, p = 0.12; OR 1.33; 95% CI 0.95–1.87) and twin assisted reproduction pregnancies (66.7% vs. 60.0%), but without significant differences.

Conclusions.  Increased obstetric risk could be observed concerning threatened preterm delivery and cesarean section rate in the study group. The perinatal outcome of singleton and twin pregnancies following assisted reproductive techniques is comparable with that of spontaneously conceived, matched pregnancies.
Relationship between bone mineral density changes in pregnancy and maternal and pregnancy characteristics: a longitudinal study
Authors: To William W. K. , Wong Margaret W. N. , Leung Tsin‐Wah
Published: August 2003

Objective.  The study aims to verify whether a progressive fall in bone mineral density (BMD) values can be demonstrated using quantitative ultrasound measurements of the os calcis. The BMD change during the pregnancy was then correlated with other maternal and pregnancy characteristics to identify any high‐risk factors for bone loss in pregnancy.

Methods.  Consecutive patients were recruited from a low‐risk obstetric clinic over a period of 9 months. BMD measurements were performed at the os calcis before 18 weeks, between 28 and 32 weeks, and at 36–38 weeks using a Hologic Sahara Clinical Bone Sonometer system. A computer‐derived BMD value was obtained with each measurement. Body fat composition was also measured using a Tanita 501 bioimpedance assay system.

Results.  In a cohort of 780 patients, a mean fall in BMD of 0.040 g/cm2 was demonstrable across the trimesters. The difference in BMD across the three serial measurements was highly significant (p < 0.001). Univariate analysis showed that those with a low initial BMD, glucose intolerance and high body fat accumulation weight gain during the pregnancy had lower BMD loss, while gestational hypertension and obesity had no impact on the degree of BMD loss. Entering these parameters in a logistic regression analysis showed that the impact of glucose intolerance was lost, but that the other factors remained significant. A linear regression model of quantitative variables showed that only fat accumulation (p = 0.03) and early pregnancy BMD values (p < 0.001) remained significant factors associated with BMD loss.

Conclusion.  A gradual fall in BMD was demonstrable using ultrasound measurement of the os calcis from early to late pregnancy. Of the various parameters identified as significant factors affecting BMD loss in pregnancy, a low initial BMD in early pregnancy and high body fat accumulation during pregnancy appeared to be related to lower BMD loss.
Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: A prospective study
Authors: Wensveen Celesta , Kagie Marjolein , Veldhuizen Roel , Groot Christianne De , Denny Lynette , Zwinderman Koos , Trimbos Baptist
Published: August 2003

Background.  (1) To assess the prevalence of histologically confirmed cervical intraepithelial neoplasia in patients with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance. (2) To evaluate the role of colposcopy and the presence of human papillomavirus in detecting underlying cervical intraepithelial neoplasia.

Materials and methods.  In this prospective cohort, 148 women with atypical squamous or glandular cells of undetermined significance were evaluated by colposcopy, histological sampling, and human papillomavirus deoxyribonucleic acid testing.

Results.  Histological diagnosis of ≥ cervical intraepithelial neoplasia II was found in 10/148 women. Women with a histological ≥ cervical intraepithelial neoplasia II had a higher prevalence of ≥ two abnormal quadrants (90% vs. 38%≤ cervical intraepithelial neoplasia I, p = 0.002) and of high/intermediate‐risk human papillomavirus (90% vs. 42% ≤ cervical intraepithelial neoplasia I, p = 0.005).

Conclusion.  Our study shows that premalignant lesions of the cervix were present in 7% of the patients with a cytological diagnosis of atypical squamous or glandular cells of undetermined significance. Colposcopy and human papillomavirus deoxyribonucleic acid testing are both important parameters in detecting ≥ cervical intraepithelial neoplasia II.
Human Seminal Plasma Antibody‐Binding Proteins
Authors: Chiu W. W. C. , Chamley L. W.
Published: August 2003

Problem: The physiological role of antibody‐binding proteins in human seminal plasma and the potential role of these proteins in infertility is relatively unknown.

Method of study: Literature on antibody‐binding proteins.

Results: Human seminal plasma has a diverse effect on immune function of the reproductive tracts. This review describes (1) the presence of receptors like proteins that can react with monoclonal antibodies against Fcγ receptors III (Fcγ RIII) but are distinctly different from Fcγ RIII; (2) IgG binding factors (IgGBF), a group of low molecular weight proteins that are capable of binding human IgG; (3) other proteins that can bind antibodies, such as prolactin‐inducible protein and three other novel proteins that we have discovered. These proteins potentially all have the ability to reduce the interactions between antisperm antibodies and effector components of the immune system, such as phagocytic cells.

Conclusions: Human seminal plasma contains proteins that can bind antibodies. However, to date our knowledge of these proteins especially, whether they have a physiological role in either the male and female reproductive tracts is limited.
Anti‐annexin A5 Antibodies in Reproductive Failures in Relation to Antiphospholipid Antibodies and Phosphatidylserine
Authors: Arai T. , Matsubayashi H. , Sugi T. , Kondo A. , Shida M. , Suzuki T. , Izumi S.‐I. , McIntyre J. A. , Makino T.
Published: August 2003

Problem: The presence of IgG anti‐annexin A5 (IgGαA5) and/or antiphospholipid antibodies (aPL) are risk factors associated with recurrent spontaneous abortion. Problems are whether IgA anti‐annexin A5 (IgAαA5) is pathogenic, and how IgGαA5 works.

Method of study: Blood samples from 238 patients with early recurrent spontaneous abortion, 48 patients with recurrent in vitro fertilization‐embryo transfer failure, 179 non‐pregnant women and 120 pregnant controls were tested for IgAαA5 by enzyme‐linked immunosorbent assay. We also determined if IgGαA5 appeared coincident with aPL. The antigenic epitope(s) recognized by IgGαA5 was investigated.

Results: We observed no difference between patients and controls for IgAαA5. The prevalence of IgGαA5 was not different statistically between patient samples with or without aPL. Patient IgGαA5 bound annexin A5 when the latter was free/unbound but not when annexin A5 was associated with phospholipid.

Conclusions: The IgAαA5 does not appear to be pathogenic. IgGαA5 works to make a complex with annexin A5 without relation to aPLs, which may reduce annexin A5 available for binding to trophoblast.
Expression of Leptin Receptor Isoforms in vitro: Lack of Effects of Leptin on Endometrial Cytokine and MMP Production
Authors: Quinton N. D. , Laird S. M. , Tuckerman E. M. , Cork B. A. , Li T. C. , Blakemore A. I. F.
Published: August 2003

Problem: Leptin has a key role to play in human female reproduction. Its receptor is expressed highly throughout the reproductive tract. Cytokines have an important role in preparing the endometrium for implantation and leptin is known to modulate cytokine production in other tissues. We, therefore, investigated the possible role of leptin in endometrial growth and function.

Method of Study: Reverse transcriptase polymerase chain reaction and immunocytochemistry were used to determine the pattern of expression of leptin receptor isoforms in primary human endometrial epithelial and stromal cells in culture. The effect of leptin on cell growth and on the production of cytokines [Leukaemia Inhibitory Factor (LIF), interleukin 6 and tumour necrosis factor‐α] and matrix metalloproteinases (MMP) (MMP2 and MMP‐9) was also investigated.

Results: Expression of the long form of the leptin was restricted to the cultured endometrial, epithelial cells. Both cultured endometrial stromal and epithelial cells expressed the short and variant isoforms of the receptor. Incubation of epithelial and stromal cell cultures with varying concentrations of leptin (0–1000 ng/mL) had no significant effect on cell growth or levels of MMP‐2 or MMP‐9 production. Leptin also had no significant effect on cytokine production by epithelial cells.

Conclusions: This study shows for the first time, the presence of leptin receptor isoforms on endometrial, epithelial and stromal cells in culture. Leptin had no effect on cytokine and MMP production by these cells. However, it is possible that leptin affects other factors within the endometrium not investigated here.
Enhancement of Immunogenicity of Jeg3 Cells by Ectopic Expression of HLA‐A*0201 and CD80
Authors: Koc Serpil , Kather Angela , Markert Udo R. , Dürst Matthias , Schneider Achim , Kaufmann Andreas M.
Published: August 2003

Problem: The choriocarcinoma cell line Jeg3 suppresses immunity in vitro by secretion of soluble factors like leukemia inhibitory factor suppressing leukocyte activation. The cells lack expression of classical human leukocyte antigen (HLA)‐A and ‐B alleles but express some HLA‐C, and non‐classical HLA‐G and ‐E. Upon binding to killing inhibitory receptor on natural killer (NK) cells, HLA‐G prevents activation of cytolytic activity. We investigated whether Jeg3 cells are capable of immune stimulation after complementation with classical HLA and T cell costimulatory signal CD80.

Method of study: Jeg3 cells were transduced to express HLA‐A*0201 and/or CD80. Parental Jeg3 or transfectants Jeg3‐A2, Jeg3‐CD80 or Jeg3‐CD80‐A2 were used to stimulate allogeneic resting and activated peripheral blood lymphocytes (PBL). The different cell lines were loaded with a HLA‐A2‐restricted Epstein‐Barr virus (EBV) recall antigen peptide epitope and antigen presenting ability was examined. T cell lines specific for Jeg3 and transfectants were generated from HLA‐A2 matched and nonmatched donors and compared for expansion, phenotypes and cytolytic activity.

Results: While all Jeg3 cell lines induced only marginal proliferation of resting T cells, phytohemagglutinin (PHA)‐activated T cells were stimulated by CD80 or CD80‐A2 expressing Jeg3. Only the transfectant Jeg3‐CD80‐A2 was capable of specific T cell stimulation by EBV recall antigen presentation. T cell lines of HLA‐A2 non‐matched donors stimulated with the Jeg3 transfectants showed significant expansion only when HLA‐A2 and the costimulus CD80 were present. T cells from HLA‐A2 positive donors did not expand significantly or differentially. No NK cells grew under any condition. In Jeg3‐CD80‐A2 stimulated T cells lines CD8+ cells expanded preferentially. These T cells exerted cytolytic activity toward all Jeg3 cell lines.

Conclusion: Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by Jeg3 cells when classical HLA‐ and/or costimulatory signals are present on the cells.
Placental Lesions Caused by Experimental Infection of Sprague–Dawley Rats with Mycoplasma Pulmonis
Authors: Peltier Morgan R. , Richey Lauren J. , Brown Mary B.
Published: August 2003

Problem: Sprague–Dawley (SD) rats infected during pregnancy with Mycoplasma pulmonis display adverse pregnancy outcomes that are similar to those observed in women with chorioamnionitis and may provide a good model system for this disease. The placental lesions caused by this microorganism, however, have not been thoroughly characterized.

Method of study: Rats were infected with 107 colony‐forming units (CFU) M. pulmonis or vehicle control on gestation day (gd) 14 and were euthanized on gd 16–18. Tissues were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 4 μm, and stained with hematoxylin and eosin (H & E). The slides were coded and examined by a blinded pathologist using light microscopy.

Results: Infection with M. pulmonis was associated with necrosis of trophoblast giant cells at gd 18. Significantly more neutrophils were observed in the decidual region of the apex of the placenta in M. pulmonis infected animals. The vast majority of neutrophils, however, were observed in the decidua in the lateral regions of the placenta and in the adjacent endometrium.

Conclusions: Infection of SD rats with M. pulmonis resulted in histological placentitis similar to that described in deciduitis of humans and represents a good model system for investigations into the pathophysiology of intrauterine infection. The influx of neutrophils seems to migrate from the endometrium towards the lateral regions of the placenta near Reichert's membrane and the divergence of the parietal yolk sac.
Cytokines, implantation and early abortion: re‐examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept
Authors: Chaouat Gérard , Lédée‐Bataille Nathalie , Zourbas Sandrine , Ostojic Sasa , Dubanchet Sylvie , Martal Jacques , Frydman René
Published: August 2003

Problem: Human in vitro fertilization (IVF) embryo transfer is accompanied by a low implantation rate even after a very successful IVF, and there are a certain number of ‘idiopathic sterilities’ which are due to repeated implantation failures. In the very same vein, the question of improving implantation rates is of prime importance in agricultural research to improve the management of livestock. Pre‐implantation prenatal diagnosis cannot be accomplished in individuals who have a high rate of implantation failure, whether women undergoing IVF, or animals, during genetic cloning. Implantation cytokine networks need to be known in such a perspective.

Methods: We review the evolution and theories in reproductive immunology, briefly deal with the complexity of implantation as a step by step developmental event, and then present some of our recent data in mice and human.

Conclusions: We conclude that the T helper cell type 1/2 (Th1/Th2) paradigm, as useful as it has been to explain pregnancy, is no longer sufficient in view of the emerging complexity of the cytokine network at the materno‐fetal interface. This is peculiarly true for implantation, which, as a step by step developmentally regulated process, involving inflammatory molecules, cannot fit into such a scheme.
Evaluation of Myeloid and Lymphoid Dendritic Cells in Peritoneal Fluid in Women with Non‐malignant Ovarian Tumors
Authors: Wertel Iwona , Kotarski Jan , Roliński Jacek , Bojarska‐Junak Agnieszka , Gogacz Marek
Published: August 2003

Problem: Identification of myeloid and lymphoid dendritic cells (DCs) in peritoneal fluid (PF) and peripheral blood (PB) of patients with ovarian pathology.

Method of study: PF and PB were collected from 60 patients who underwent laparoscopy because of non‐malignant ovarian tumors. Mononuclear cells were separated by gradient centrifugation. The cell surface antigens were determined by flow cytometry using monoclonal antibodies.

Results: Both myeloid and lymphoid DCs were detected in PF and PB of women with ovarian tumors. The percentage of myeloid DCs was significantly higher in PF than in PB. The concentration of PF myeloid DCs was the highest (P < 0.05) in patients with dermoid cysts (0.67 × 106/mL PF) in comparison with the other studied groups, excluding patients with normal pelvis.

Conclusions: Domination of myeloid and not lymphoid cells in PF may support the hypothesis that local PF immune disturbances may play a role in some non‐malignant ovarian pathology.
Effect of Antisperm Antibodies Present in Human Follicular Fluid upon the Acrosome Reaction and Sperm–Zona pellucida Interaction
Authors: Marín‐Briggiler Clara I. , Vazquez‐Levin Mónica H. , Gonzalez‐Echeverría Fernanda , Blaquier Jorge A. , Miranda Patricia V. , Tezón Jorge G.
Published: August 2003

Problem: To determine the ability of IgGs isolated from follicular fluids (hFFIgGs) to induce the acrosome reaction (AR) in human spermatozoa and to inhibit sperm–zona pellucida (ZP) interaction.

Method of study: Incubation of capacitated spermatozoa with hFFIgGs (n = 40) and assessment of their effect on the AR or hemizona (HZ) assay in a condition that allows sperm–ZP interaction, avoiding acrosomal exocytosis.

Results: hFFIgGs from different women varied in their ability of inducing the AR. Those hFFIgGs with the highest AR‐inducing capacity evoked the exocytotic response in most of the different sperm donors tested [high Induction Frequency (IF)]. Some of these antibodies were also able of inhibiting sperm binding to ZP [low HZ Index (HZI)]. A significant correlation was found between the IF and the HZI for each hFFIgG.

Conclusions: Human follicular fluid contains antibodies capable of inducing the AR and inhibiting sperm–ZP binding, suggesting that they could be directed towards ZP receptors. hFFIgGs would constitute a tool for the identification of sperm entities involved in fertilization.
GM‐CSF and Pregnancy: Evidence of Significantly Reduced Blood Concentrations in Unexplained Recurrent Abortion Efficiently Reverted by Intravenous Immunoglobulin Treatment
Authors: Perricone Roberto , De Carolis Caterina , Giacomelli Roberto , Guarino Maria D. , De Sanctis Giuliana , Fontana Luigi
Published: August 2003

Problem: Certain Th‐2 cytokines and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) are propitious for the success of pregnancy and recurrent spontaneous abortion (RSA) is often characterized by a failure of Th‐2 type responses. These considerations as well as the use of intravenous immunoglobulin (IVIg) in RSA induced us to evaluate the levels of GM‐CSF in normal pregnancies, in pregnant women affected with unexplained RSA and the effects of IVIg treatment.

Method of study: Peripheral blood free GM‐CSF was measured by means of a sandwich enzyme immunoassay in 39 healthy women (13 non‐pregnant, 26 pregnant) and in 53 RSA patients (11 non‐pregnant, 42 pregnant). In 14 pregnant RSA patients GM‐CSF was studied also after the very first IVIg infusion (0.5 g/kg body weight).

Results: In healthy women we found a significant increase of GM‐CSF during pregnancy, in pregnant RSA patients such an increase was not detected. After IVIg, GM‐CSF concentrations were almost doubled.

Conclusions: GM‐CSF is found increased in normal pregnancy and is very low during pregnancy in RSA. IVIg infusions are capable of increasing GM‐CSF in pregnant recurrent aborters.
Identification of Possible Mediators of Embryonic Mortality Caused by Mastitis: Actions of Lipopolysaccharide, Prostaglandin F2α, and the Nitric Oxide Generator, Sodium Nitroprusside Dihydrate, on Oocyte Maturation and Embryonic Development in Cattle
Authors: Soto P. , Natzke R. P. , Hansen P. J.
Published: August 2003

Problem: Mastitis and immunization against constituents of organisms causing mastitis can reduce fertility of cattle and sheep, respectively. For the current experiments, it was hypothesized that these effects are mediated via actions of lipopolysaccharide (LPS), prostaglandin F2α (PGF2), and nitric oxide on oocyte maturation and embryonic development.

Method of study: To evaluate effects on oocyte maturation, oocytes were matured with various concentrations of LPS, PGF2α, or the nitric oxide (NO) generator, sodium nitroprusside (SNP). Following maturation, oocytes were fertilized and cultured until day 8 after fertilization. To test effects on embryo growth, oocytes were matured and fertilized and cultured after fertilization with LPS, PGF2α, or SNP.

Results: Addition of 100 and 1000 ng/mL LPS and 50 and 100 ng/mL PGF2α to oocyte maturation medium reduced the proportion of oocytes that became blastocysts at day 8 after fertilization. When added after fertilization, in contrast, neither LPS nor PGF2α reduced development to the blastocyst stage. Unlike for LPS and PGF2α, addition of SNP during oocyte maturation was without effect on the proportion of oocytes that became blastocysts at day 8 after fertilization. However, addition of 10 μm SNP to culture medium after fertilization completely prevented development to the blastocyst stage while 0.1 and 1 μm SNP did not affect development.

Conclusions: Results indicate that increased local concentrations of LPS, PGF2α, and NO can have deleterious consequences on oocyte function (LPS, PGF2α) and embryonic development (NO). Thus, these molecules are putative mediators of effects of infectious disease or inflammation, including mastitis, on fertility of cattle.
Placental Trophoblast from Successful Human Pregnancies Expresses the Tolerance Signaling Molecule, CD200 (OX‐2)*
Authors: Clark David A. , Keil Anja , Chen Zhiqi , Markert Udo , Manuel Justin , Gorczynski Reginald M.
Published: August 2003

Problem: Th1 cytokine‐dependent abortions in the CBA × DBA/2 mouse model have been linked to down‐regulation of expression of the CD200 (OX‐2) ‘tolerance’ signal on trophoblast and in decidua prior to onset of the abortion process. Abortions could be prevented by administration of a soluble CD200. Is CD200 expressed on trophoblast in successful human pregnancy?

Method of study: As one cannot easily obtain trophoblasts in large quantities from successful human pregnancies in the first trimester prior to the onset of the abortion process at 6 weeks gestation, we examined as a first step, trophoblast isolated from term placentae (i.e. successful pregnancies). CD9− trophoblasts were isolated by affinity column and stained for intracellular cytokeratin, and surface CD200 using PE‐anti‐human CD200 monoclonal antibody. mRNA was extracted from CD9+ and CD9− cells and tested by reverse transcription–polymerase chain reaction for CD200 mRNA. CD9− placental cells were separated by velocity sedimentation and test for CD200‐dependent suppression of an allogeneic human mixed lymphocyte culture where cytotoxic T cell (CTL) generation, and Th1 → Th2 cytokine production shift were measured.

Results: CD9− but not CD9+ placental cell populations contained cells with mRNA for CD200, both a normal length transcript and a truncated transcript. Flow cytometry showed a CD200+ cytokeratin+ moderate‐to‐large‐sized cell population compatible with trophoblasts and a smaller subset of cytokeratin− cells that expressed CD200 at normal and at high levels. The moderate‐sized population proved most potent at inhibiting CTL generation and caused a Th1→Th2 cytokine shift. These effects were blocked by monoclonal anti‐CD200.

Conclusions: A subpopulation of cytokeratin+ placental trophoblasts express bioactive CD200 able to alter maternal immune responses in a favorable (Th2 > Th1) direction. Two populations of CD200+ small‐ and medium‐small‐sized cytokeratin− placental cells remain to be identified. Studies of karyotyped first trimester elective termination and spontaneous miscarriage tissues are needed.
Radioimmunodiagnosis of lymph node metastases in head and neck cancer
Authors: de Bree R , Roos JC , Verel I , van Dongen GAMS , Snow GB
Published: August 2003

Introduction:  Reliable staging of the neck remains a diagnostic challenge in head and neck squamous cell carcinoma (HNSCC) patients. Monoclonal antibodies (MAbs) directed against tumour‐associated antigens can be used for selective tumour targeting. When labelled with a γ‐emitting radionuclide like 99mTechnetium, such MAbs can be used for tumour detection by radioimmunoscintigraphy (RIS).

Objective:  The aim of this study was to assess the potential of RIS for the detection of lymph node metastases in HNSCC patients.

Patients and methods:  In 49 patients with HNSCC, who were scheduled to undergo surgery including neck dissection, RIS using 99mTc‐labelled squamous cell specific MAb E48 or U36 administered intravenously was compared with clinical palpation, computed tomography (CT), magnetic resonance imaging (MRI) and histopathological outcome.

Results:  RIS detected lymph node metastases in 35 of 51 positive sides (sensitivity 69%). Interpretation of RIS was correct in 47 of 65 sides (accuracy 72%). Accuracy of palpation, CT and MRI were comparable. Immunohistochemical staining of lymph node metastases missed by RIS showed that the injected MAb had targeted these small tumour deposits but these were not visualized.

Conclusions:  RIS at its current stage of development is not superior to CT or MRI for the detection of lymph node metastases. As small tumour deposits were probably not visualized because of the limited sensitivity and/or spatial resolution of the gamma camera, positron emission tomography (PET) using MAbs labelled with positron emitters may improve the detection. As MAb‐PET studies in an animal model showed promising results we will soon start a clinical MAb‐PET study.
Changes of α1‐protease inhibitor and secretory leukocyte protease inhibitor levels in gingival crevicular fluid before and after non‐surgical periodontal treatment
Authors: Nakamura‐Minami M , Furuichi Y , Ishikawa K , Mitsuzono‐Tofuku Y , Izumi Y
Published: August 2003

Objectives: The possible contribution of α1‐protease inhibitor (α1‐PI) and secretory leukocyte protease inhibitor (SLPI) in gingival crevicular fluid (GCF) to predict the periodontal disease activity was evaluated.

Design: GCF samples were collected at each site before scaling and root planning (SRP), 2 and 4 weeks after SRP.

Subjects And Methods: Forty‐one sites that initially bled on probing in 21 patients with moderate to severe periodontitis were studied. Sites were classified according to the presence or absence of bleeding on probing (BOP) at 4 weeks. In GCF α1‐PI and SLPI were determined by enzyme‐linked immunosorbent assays.

Results: A significant decrease was observed in α1‐PI at 2 and 4 weeks in BOP(−) sites and at 4 weeks in BOP(+) sites. SLPI significantly increased at 2 weeks in BOP(+) site, while SLPI did not significantly differ at both time points in BOP(−) sites and at 4 weeks in BOP(+) sites. GCF α1‐PI was significantly less at 2 weeks in BOP(−) than in BOP(+) sites.

Conclusion: At 2 weeks GCF α1‐PI may reflect the healing response of the periodontal tissues following non‐surgical periodontal treatment. GCF SLPI levels may be influenced by healing.
Characterization of the development of ectopic chondroid/bone matrix and chondrogenic/osteogenic cells during osteoinduction by rhBMP‐2: a histochemical and ultrastructural study
Authors: Nakagawa T , Sugiyama T , Shimizu K , Murata T , Narita M , Nakamura S , Tagawa T
Published: August 2003

Objective: To investigate the characteristics of ectopic chondroid/bone matrix and chondrogenic/osteogenic cells induced by recombinant human bone morphogenetic protein‐2 (rhBMP‐2).

Materials and methods: rhBMP‐2 (5 μg) combined with atelocollagen was implanted into calf muscles of rats and removed on days 7, 10, 14, 21, or 28. Tissue sections were examined using: (i) hematoxylin/Alcian blue/Sirius red stain, (ii) enzyme histochemistry for alkaline phosphatase (ALP) and tartrate‐resistant acid phosphatase activity, (iii) immunohistochemistry for types I, II, and X collagen, and (iv) electron microscopy.

Results: On day 7, numerous fibroblast‐like cells with ALP activity were present on the pellet rim. On day 10, chondroid matrix (CM) had formed, contained both type I collagen and proteoglycans, and often continued into the BMP pellet. On day 14, bone‐like matrix formed around hypertrophic chondrocytes simultaneously with endochondral ossification. Coexpression of types I and II collagen within chondrocytes and osteocytes was observed throughout the time course of the experiment.

Conclusion: These results suggest that fibroblast‐like cells invading the pellet differentiate into chondrocytes and form CM under the scaffold of the carrier component. It appears that some chondrocytes change their phenotype to produce the bone‐like matrix and remain within the endochondral bone. This process enables rapid osteogenesis to occur.
Immunohistochemical demonstration of p63 in DMBA‐induced hamster buccal pouch squamous cell carcinogenesis
Authors: Chen YK , Hsue SS , Lin LM
Published: August 2003

Objectives: Abnormalities in the p53 gene are regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 at the 1p36 region and p63 at the 3q27‐29 region, have recently been identified. They share considerable sequence homology with p53 in the transactivation, DNA binding, and oligomerization domains, indicating possible involvement in carcinogenesis. To our knowledge, however, p63 expression in experimental oral carcinogenesis has not been studied.

Materials and methods: Immunohistochemical analysis of p63 protein expression was performed in 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced hamster buccal pouch squamous cell carcinogenesis. Fifty outbred, young (6 weeks), male, Syrian golden hamsters (Mesocricatus auratus) were randomly divided into three experimental groups (each consisting of 10 3‐, 9‐ and 15‐week DMBA treated animals), and two control groups (with 10 animals in each). The pouches of the three experimental groups were painted bilaterally with a 0.5% DMBA solution three times a week. The treatment protocol for animals in one of the control groups was identical with only mineral oil applied, while the other control group remained untreated throughout the experiment.

Results: In all of the untreated and mineral oil‐treated pouch mucosa, nuclear positivity for p63 was mainly observed in the basal/parabasal cell layers. The p63 nuclear positivity extended from the basal/parabasal layers to the whole epithelial layers in the 3‐ and 9‐week DMBA‐treated pouch mucosa. Furthermore, the positive nuclear‐stain cells were randomly distributed throughout the entire epithelial layers in the 3‐ and 9‐week DMBA‐treated pouch‐mucosa specimens. In carcinomas from 15‐week DMBA‐treated pouch specimens, p63 staining was more uniform and homogeneous for the less‐differentiated tumor areas. By contrast, p63 expression was noted mainly in the peripheral cells of tumor nests in the well‐differentiated tumor areas.

Conclusions: The results of this study are consistent with those from previous analyses of p63 expression in human oral mucosa, suggesting that p63 may be associated with the regulation of epithelial differentiation and proliferation in DMBA‐induced hamster buccal pouch squamous cell carcinogenesis. Further study is required to investigate which p63 isoform(s) is/are involved in hamster buccal pouch carcinogenesis.
Oral lesions in recessive dystrophic epidermolysis bullosa
Authors: Serrano‐Martínez MC , Bagán JV , Silvestre FJ , Viguer MT
Published: August 2003

Objective:  To study the prevalence of oral lesions in 35 patients diagnosed with generalized recessive dystrophic epidermolysis bullosa (RDEBg), with a quantification of their microstomia in comparison with a control group.

Material and methods:  The presence of oral mucosal lesions and interincisal maximum oral aperture (MOA) was determined, classifying microstomia according to the method of Naylor, Douglass and Mix (1984).

Results:  Blister lesions were identified in 92% of the patients at the time of exploration – the tongue being the most affected location. Microstomia and palatal atrophy were the most prevalent sequelae (100%), while ankyloglossia, vestibular obliteration and lingual depapillation were recorded in over 90%. In 80% of the patients interincisal MOA was <30 mm (severe microstomia), while in the remaining cases maximum aperture was in the range of 31–40 mm (moderate microstomia).

Conclusions:  Blister lesions were found throughout the oral mucosa in our series of patients with RDEBg, the most frequently affected location being the tongue. These lesions in turn led to invalidating sequelae such as microstomia and ankyloglossia.
Nonsense-mediated decay breaks the circle?
Authors: GRAHAM Sheila V.
Published: August 2003

This Commentary discusses new data from the laboratory of Matthias Hentze (Schell et al., in this issue) that begins to dissect the RNA–protein and protein–protein interactions important for the process of nonsense-mediated decay (NMD). Schell and co-workers have developed a novel tool for analysis of such interactions in vivo. Using a proteomics approach, they have identified two different protein–RNA complexes that contain human Upf (up-frameshift) proteins central to the NMD process. Intriguingly, they identified a poly[A]-binding protein associated with these complexes.
POPing the fire into the pyrin?
Authors: MARIATHASAN Sanjeev , VUCIC Domagoj
Published: August 2003

Initiation of an inflammatory response requires the co-ordinated participation of proteins within a scaffold in the cytosol of responding cells. The scaffold proteins contain members of a newly discovered family of pyrin-domain adaptor proteins that regulate complex assembly for initiation of nuclear factor κB and interleukin-1β signalling. A paper in this issue of the Biochemical Journal by Stehlik et al. identifies a new member of the pyrin family that may control signalling by sequestering pro-inflammatory components, shedding light on the origin of human inflammatory disorders.
Unloading joints and rockfalls in Norway's fiordlands
Authors: Waltham Tony
Published: August 2003

When overburden is removed by erosion, rock relaxes towards the surface and develops new fractures. These are then the focus of slope failures that are common and sometimes disastrous in Norway's mountain regions.
Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity
Authors: Hellman Karin , Roos Ewa , Österlund Anna , Wahlberg Anneli , Gustafsson Lars L. , Bertilsson Leif , Fredrikson Sten
Published: August 2003

Aims  To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment.

Methods  CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy‐debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN‐β (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed.

Results  There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI −0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI −0.44, 1.02) before and during regular IFN‐β treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN‐β treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10).

Conclusions  IFN‐β treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN‐β.