Outcome in obstetric care related to oxytocin use. A population-based study.

Background: The purpose of this study was to investigate the delivery outcome in relation to oxytocin use in labor.

Methods: We studied 106,755 deliveries from 1995 to 2002 in the Perinatal Revision South, a population-based register comprising information from 10 hospitals in southern Sweden.

Results: Oxytocin use in labor increased from 27.

Fetal growth and onset of delivery: a nationwide population-based study of preterm infants.

Objective: This study was undertaken to assess whether deviations from normal fetal growth are associated with spontaneous preterm delivery.

Study Design: A population-based study was performed, using Swedish Medical Birth Register data from 1991 through 2001. The total population comprised 1,007,648 singleton births.

gp130 dimerization in the absence of ligand: preformed cytokine receptor complexes.

It is established that cytokine receptors signal after ligand binding as homo- or hetero-dimers in heteromeric complexes, but it is unclear, when dimerization occurs. To investigate gp130 dimerization, we performed co-precipitation experiments with the endogenous cytokine receptors gp130 and leukemia inhibitory factor receptor (LIF-R) and with gp130 variants carrying two different C-terminal peptide tags. Furthermore, fluorescence resonance energy transfer (FRET) was employed to detect dimerization of two fluorescent-tagged gp130 variants.

Physiological development of a mixed metabolic and respiratory umbilical cord blood acidemia with advancing gestational age.

Objective: To investigate respiratory and metabolic components of gestational age-dependent umbilical cord blood gas changes.

Study Design: Cord blood gases were determined in 1336 vigorous singletons with uncomplicated cephalic vaginal delivery at 37-43 weeks. Linear regression analysis and non-parametric statistics were used with a P < 0.

Implementation of new medical techniques: experience from the Swedish randomized controlled trial on fetal ECG during labor.

Background: In a large Swedish multicenter randomized controlled trial (RCT) on intra partum fetal monitoring with automatic analysis of fetal ECG waveform (STAN) in combination with cardiotocography (CTG) (4966 parturients, 300 obstetricians and midwives managing the patients), interim analysis revealed protocol violations. By a post hoc analysis of the results over time, factors affecting the acceptance of the new technique were analyzed.

Methods: The rates of primary and secondary outcome measures (fetal outcome, operative deliveries) were compared in the two study groups (CTG + ST and CTG only).

New developments in IL-6 dependent biology and therapy: where do we stand and what are the options?

Interleukin-6 (IL-6) is a four-helical protein which, on target cells, binds to a specific IL-6-receptor and two molecules of the promiscuous signal transducing protein gp130. Structure-function analysis defined three molecular contact sites between IL-6 and its receptor subunits. Using this information, competitive antagonistic proteins as well as hyperagonistic proteins were developed.

Murine liver antigen presenting cells control suppressor activity of CD4+CD25+ regulatory T cells.

CD4(+)CD25(+) regulatory T cells (Treg) are important mediators of peripheral immune tolerance; however, whether Treg participate also in hepatic immune tolerance is not clear. Therefore, we tested the potential of Treg to suppress stimulation of CD4(+) T cells by liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC), or hepatocytes. In the absence of Treg, all 3 types of liver cells could stimulate CD4(+) T cell proliferation; in the presence of Treg, however, CD4(+) T cell proliferation was suppressed.

Preterm birth in Sweden 1973-2001: rate, subgroups, and effect of changing patterns in multiple births, maternal age, and smoking.

Background: The objectives of this report are to evaluate changes in the preterm birth rate in Sweden 1973-2001. Furthermore, describe the proportion of spontaneous and indicated preterm births and assess risk factors for the subgroups of preterm birth during the period from 1991 to 2001.

Methods: A population-based register study of all births occurring in Sweden from 1973 to 2001 registered in the Swedish Medical Birth Register was designed.

Dynamics of the gp130 cytokine complex: a model for assembly on the cellular membrane.

Cytokines of the interleukin-6 (IL-6)-type family all bind to the glycoprotein gp130 on the cell surface and require interaction with two gp130 or one gp130 and another related signal transducing receptor subunit. In addition, some cytokines of this family, such as IL-6, interleukin-11, ciliary neurotrophic factor, neuropoietin, cardiotrophin-1, and cardiotrophin-1-like-cytokine, interact with specific ligand binding receptor proteins. High- and low-affinity binding sites have been determined for these cytokines.

The IL-6R alpha chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo.

The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to those in controls.

Development of a monoclonal antibody-based enzyme-linked immunoabsorbent assay for the binding of gp130 to the IL-6/IL-6R complex and its competitive inhibition.

The proinflammatory cytokine IL-6 binds to the membrane bound or soluble IL-6 receptor (IL-6R) and activates an intracellular signaling cascade after complex formation with two gp130 molecules. These mediate general homeostasis and orchestrates the immune response during disease. Trans-signalling via the soluble IL-6R has importance for the development and maintenance of human diseases like Crohn's disease, peritonitis and rheumatoid arthritis.

Increased risk of perinatal/neonatal death in infants who were smaller than expected at ultrasound fetometry in early pregnancy.

Objectives: To investigate if there is an association between perinatal/neonatal death and a discrepancy between gestational age by ultrasound fetometry in early pregnancy (GA(U)) and gestational age by last menstrual period (GA(LMP)), and to investigate possible causes for such an association.

Methods: The Swedish Medical Birth Registry was used to identify singleton pregnancies with information available on GA(LMP) and GA(U) that were delivered in Sweden between 1990 and 2000. A total of 718 011 pregnancies was included and information on the pregnancy and delivery was obtained from the National Board of Health.

The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis.

Interleukin-6 (IL-6) is involved in the growth and differentiation of numerous cell types. In the skin it is produced primarily by keratinocytes. The transcription factor STAT3 is activated by cytokines of the IL-6 family.

The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10.

The novel CXC-chemokine ligand 16 (CXCL16) functions as transmembrane adhesion molecule on the surface of APCs and as a soluble chemoattractant for activated T cells. In this study, we elucidate the mechanism responsible for the conversion of the transmembrane molecule into a soluble chemokine and provide evidence for the expression and shedding of CXCL16 by fibroblasts and vascular cells. By transfection of human and murine CXCL16 in different cell lines, we show that soluble CXCL16 is constitutively generated by proteolytic cleavage of transmembrane CXCL16 resulting in reduced surface expression of the transmembrane molecule.

Relation between oculo-auriculo-vertebral (OAV) dysplasia and three other non-random associations of malformations (VATER, CHARGE, and OEIS).

Using a statistical methodology, we aimed to identify a group of probable cases of oculo-auriculo-vertebral (OAV) dysplasia and to investigate possible relationships between different patterns of congenital malformations. Among 5,260 infants with multiple malformations collected from 4 large registers of congenital malformations, we identified 312 probable OAV cases. With the same technique, we have earlier defined epidemiological delineations of three other well-known non-random associations of congenital malformations (CHARGE, VATER, and OEIS).

Depletion of cellular cholesterol and lipid rafts increases shedding of CD30.

CD30, a lymphoid activation marker, is shed into the cell environment after endoproteolytic cleavage of its ectodomain. Soluble (s)CD30 is able to suppress the Th1-type immune response. Because high serum levels of sCD30 and cholesterol-lowering drugs seem to be beneficial in some Th1-type autoimmune diseases, we focused on a link between CD30 shedding and the amount of cellular cholesterol.

Ictal SPECT in clinical perisylvian syndrome.

In the congenital bilateral perisylvian syndrome, pseudobulbar symptoms, cognitive deficits and cortical malformations in the perisylvian region are typical features. We report two initially magnetic resonance imaging (MRI) negative patients from our epilepsy surgery program that shared the same seizure and ictal SPECT characteristics suggesting seizure onset localized in the perisylvian region. In one patient, reevaluation revealed perisylvian cortical malformation on MRI while in the other patient MRI was normal.

Gestational age-dependent reference values for pH in umbilical cord arterial blood at term.

Objective: Despite a change of fetal physiologic and biochemical functions with gestational age, stationary umbilical cord acid-base reference values are used as measures of obstetric care quality. The aim of this study was to assess the risk of low Apgar score relative to low pH when using stationary versus gestational age-adjusted reference values.

Methods: Umbilical artery pH was determined in 24,390 term singleton vaginal deliveries with a 5-minute Apgar score of 9 or greater.

Lack of gp130 expression in hepatocytes promotes liver injury.

Background & Aims: Interleukin 6 (IL-6) contributes via its signal transducer gp130 to the acute phase response (APR) in hepatocytes. Recent studies indicated that IL-6 is involved in the regulation of different pathophysiologic conditions of the liver. To define the IL-6-dependent intracellular pathways more specifically, we generated a hepatocyte-specific gp130 knockout mouse.

Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE).

Interleukin-6 (IL-6) activates cells by binding to the membrane-bound IL-6 receptor (IL-6R) and subsequent formation of a glycoprotein 130 homodimer. Cells that express glycoprotein 130, but not the IL-6R, can be activated by IL-6 and the soluble IL-6R which is generated by shedding from the cell surface or by alternative splicing. Here we show that cholesterol depletion of cells with methyl-beta-cyclodextrin increases IL-6R shedding independent of protein kinase C activation and thus differs from phorbol ester-induced shedding.

Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis.

Objective: To investigate if caesarean section (CS) increases the risk for childhood asthma and gastroenteritis with reference made to children born with vaginal delivery (VD).

Methods: Retrospective study of data from linked Swedish medical service registers--Medical Birth Registry (MBR) and Hospital Discharge Registry (HDR). Data were obtained from women without any background/perinatal morbidity noted, and from children without any neonatal complications.

Analysis of the leukemia inhibitory factor receptor functional domains by chimeric receptors and cytokines.

In contrast to other hematopoietic cytokine receptors, the leukemia inhibitory factor receptor (LIFR) possesses two cytokine binding modules (CBMs). Previous studies suggested that the NH(2)-terminal CBM and the Ig-like domain of the LIFR are most important for LIF binding and activity. Using the recently engineered designer cytokine IC7, which induces an active heterodimer of the LIFR and gp130 after binding to the IL-6R, and several receptor chimeras of the LIFR and the interleukin-6 receptor (IL-6R) carrying the CBM of the IL-6R in place of the COOH-terminal LIFR CBM, we could assign individual receptor subdomains to individual binding sites of the ligand.

The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion.

The CX3C chemokine fractalkine (CX3CL1) exists as a membrane-expressed protein promoting cell-cell adhesion and as a soluble molecule inducing chemotaxis. Transmembrane CX3CL1 is converted into its soluble form by defined proteolytic cleavage (shedding), which can be enhanced by stimulation with phorbol-12-myristate-13-acetate (PMA). PMA-induced CX3CL1 shedding has been shown to involve the tumor necrosis factor-alpha-converting enzyme (TACE), whereas the constitutive cleavage in unstimulated cells remains elusive.

Skewed fetal gender distribution in prolonged pregnancy: a fallacy with consequences.

Objective: Skewed gender distribution and falsely assigned gestational age lead to unnecessary or late obstetric intervention in prolonged pregnancy. The aim of this study was to examine the consequences of a fetal gender-dependent systematic 1.5-day dating error at ultrasound fetometry.