Changing trends in operative delivery performed at full dilatation over a 10-year period.

This study was a systematic anonymous audit of routinely collected data in a tertiary referral obstetric unit in London and included data from deliveries over a 10-year period (1992-2001). Data for all caesarean sections at full dilatation were collected, including maternal demographic information, the grade of operating clinician, and the place of delivery. Neonatal data collected included birth weight and umbilical arterial pH. No changes in the demographics of the population were observed. No increased rates of malposition were observed. Birth weight did not change. Increasing preference for the ventouse over forceps (ratio 0.2:1 to 1.9:1) over the decade (p = 0.002) was seen with an increased tendency to conduct the delivery in the operating theatre (p = 0.0025). Rate of caesarean section at full dilatation increased (2% by 2001). Increasing failures of operative vaginal delivery, especially using the ventouse (regression coefficient p = 0.025), and reduced attempts at instrumentation (regression coefficient p = 0.002) were seen.

The mitogen-activated protein kinase dependent expression of prostaglandin H synthase-2 and interleukin-8 messenger ribonucleic acid by myometrial cells: the differential effect of stretch and interleukin-1{beta}.

Infection and uterine stretch are the common causes of preterm labor. IL-1beta plays a key role in infection-induced preterm labor and increases prostaglandin H synthase 2 (PGHS-2) and IL-8 expression. We have shown that mechanical stretch of uterine myocytes in vitro up-regulates the expression of PGHS-2 and IL-8. In this study, we tested the hypotheses that both IL-1beta and mechanical stretch increase the myometrial expression of PGHS-2 and IL-8 via MAPK activation and that their effects are synergistic. MAPK activation was assessed in myocytes obtained from pregnant women undergoing cesarean section before the onset of labor after exposure to IL-1beta and stretch either alone or in combination. Specific inhibitors of ERK, p38, and c-Jun N-terminal kinase were used to define the role of each in the increased expression of PGHS-2 and IL-8 mRNA. We found that both IL-1beta and stretch activated all three MAPK subtypes but that they had no synergistic effect. The inhibitor studies showed that stretch-induced increases in both PGHS-2 and IL-8 mRNA expression were ERK1/2 and p38 dependent and that IL-1beta-induced increases of PGHS-2 mRNA expression were also ERK1/2 and p38 dependent, but those of IL-8 were dependent only on ERK1/2 activation. These data show that exposure of human uterine myocytes to both stretch and IL-1beta activates the MAPK system, which is responsible for the increase in PGHS-2 and IL-8 mRNA expression. We found no evidence of a synergistic effect of IL-1beta and stretch on myometrial expression of PGHS-2 and IL-8 mRNA.

Mechanical stretch of human uterine smooth muscle cells increases IL-8 mRNA expression and peptide synthesis.

Labour is associated with increased synthesis of interleukin-8 (IL-8) by the fetal membranes and myometrium, which leads to an inflammatory infiltrate. Stretch has been shown to increase the expression of contraction-associated proteins in animal models of labour and in human myocytes in vitro. In this study, we tested the hypothesis that mechanical stretch of human myometrial cells increases IL-8 messenger ribonucleic acid (mRNA) expression. We isolated myocytes from non-pregnant women undergoing hysterectomy and pregnant women undergoing Caesarean section before and after the onset of labour. Myocytes in culture were subjected to stretch of varying intensity (6-16%) and duration (1 or 6 h) using the Flexercell system. IL-8 mRNA expression was lowest in myocytes from pregnant women not in labour, intermediate in those from non-pregnant women and greatest in those from pregnant women in labour. Stretch increased IL-8 mRNA expression independent of reproductive state. The stretch-induced increase in IL-8 mRNA expression was associated with higher IL-8 levels in the culture supernatant and enhanced promoter activity. These data suggest that stretch contributes to the increase in myometrial IL-8 synthesis associated with the onset of labour in humans.

IL-1beta and IL-8 in human fetal membranes: changes with gestational age, labor, and culture conditions.

PROBLEM: Interleukin (IL)-1beta and IL-8 are associated with labor. This study aimed to characterize their concentrations in fetal membranes and any changes in these with advancing gestation and to define as to whether there are interactions between the membranes in their expression. METHOD OF STUDY: mRNA and protein content of amnion and choriodecidua at increasing gestations and before and after labor at term were quantified. Membranes were also collected before and after labor, separated, and cultured. Protein production was measured by ELISA. RESULTS: IL-1beta and IL-8 concentration increased in third trimester amnion and choriodecidua. Further increased expression of mRNA of both cytokines was found after labor in both membranes except IL-8 production by amnion. Choriodecidua produced more of each cytokine than amnion, however, no interaction between the membranes was demonstrated by culture. CONCLUSIONS: Increasing expression of IL-1beta and IL-8 in amnion and choriodecidua in the third trimester and after labor supports a role for these cytokines in the establishment of labor.

Nuclear factor-kappa B is essential for up-regulation of interleukin-8 expression in human amnion and cervical epithelial cells.

Interleukin-8 (IL-8) is a cytokine which recruits and activates neutrophils into tissue stroma. It is present in uterine tissues and its concentration increases in the third trimester and with labour. The promoter region of the IL-8 gene contains binding sites for the transcription factors, nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1) and CCAAT/enhancer-binding protein (C/EBP). These are in close proximity to each other and to the coding region of the gene. This study used site-directed mutagenesis of each of these sites to examine the relative importance of each site in IL-8 gene expression in a cervical cell line and in amnion cells obtained before and after labour. We found that the NF-kappaB site was essential for basal and IL-1beta-stimulated gene expression in all cell types. Neither of the other binding sites was consistently essential for gene expression but may have an additive role in promoter activity. We conclude that the NF-kappaB binding site is essential for up-regulation of IL-8 gene expression in these uterine cell types. An increase in IL-8 expression has been shown to occur in the uterus in association with parturition and NF-kappaB binding to the promoter may be of importance at this time.

Angiosarcoma of the mandible: a case report and review of the literature.

Angiosarcoma is a rare malignancy that is characterized by endothelial cell differentiation. In the head and neck area, most of these lesions arise in the scalps of elderly individuals. Less commonly, angiosarcomas can be found within bone. The purpose of this report is to describe an example of angiosarcoma involving the floor of the mouth and right body of the mandible. The histopathologic and immunopathologic features of these lesions are also reviewed.

Role of proximal promoter elements in regulation of renin gene transcription.

Mouse As4.1 cells, obtained after transgene-targeted oncogenesis to induce neoplasia in renal renin-expressing cells, express high levels of renin mRNA from the endogenous Ren-1(c) gene. We have used these cells to characterize the role of the Ren-1(c) proximal promoter (+6 to -117) in the regulation of renin gene transcription. It was found that 4.1 kilobases (kb) of Ren-1(c) 5'-flanking sequence, in combination with the proximal promoter, are required for strong activation (approximately 2 orders of magnitude over the basal level of the promoter alone) of the chloramphenicol acetyltransferase reporter in transfection assays. Within the 4.1-kb fragment, a 241-base pair region was identified that retains full activity in an orientation-independent manner in combination with the promoter. The resulting transcripts initiate at the normal renin start site. Electrophoretic mobility shift assays identified a sequence at approximately position -60 in the promoter region that binds nuclear proteins specific for renin-expressing As4.1 cells. Mutations in this sequence, which disrupt binding of nuclear protein(s), completely abolish activation of transcription by the 4. 1-kb fragment. Activation of transcription by the 241-base pair enhancer was still observed, although it was diminished in magnitude (60-fold over the mutated promoter alone). We present a model derived from the current data that suggests that regulation of renin expression is achieved through cooperation of transcription factors binding at the proximal promoter element and a distal enhancer element to abrogate or override the effects of an intervening negative regulatory region.

Species differences in binding of submandibular nuclear proteins to renin promoter DNA.

1. Renin is highly expressed in submandibular gland (SMG) of mouse, which has two genes, Ren-1d and Ren-2d, but not at all in rat SMG. Differences in nuclear protein binding to renin promoter DNA were, therefore, explored. 2. Rat -169 to +23 renin DNA formed complexes with both mouse and rat extract, whereas a corresponding fragment of mouse Ren-1d DNA (-121 to +4) bound with rat extract, but much less so with mouse extract. Rat extract bound a -704 to -450 fragment of the Ren-1d promoter. For Ren-2d -578 to -383 and -786 to -718 DNA bound with mouse extract and -383 to +11 and -664 to -578 DNA bound with rat extract. 3. The results support a role for differences in presence or binding of species-specific trans-acting factors in the differential regulation of the renin gene in SMG of mouse and rat. Strong binding near the rat RNA polymerase II binding site could repress transcription in rat SMG, and binding peculiar to the Ren-2d B2 element might contribute to high expression in mouse SMG.

Mutagenesis and regulation of the cysJ promoter of Escherichia coli K-12.

The cysJ promoter of Escherichia coli K-12, which is positively controlled by the CysB regulatory protein, was localized through the formation of a fusion of cysJ, the gene encoding NADPH-cytochrome c reductase with lacZ. The position of the transcription start point was determined and the orientation of transcription was shown to be counterclockwise on the E. coli K-12 map. Oligodeoxyribonucleotide-directed mutagenesis of the inferred -10 and -35 regions indicated that both sites could be altered to produce promoter 'down' mutations. When the -10 region was made to agree with the -10 consensus sequence, there was increased function under conditions of repression (that is, in the presence of cysteine). Upstream deletions, as well as mutations in a region proposed to be involved in binding of the CysB regulatory protein, identified sequences important for promoter activity from -90 to -78 and from -71 to -66. By comparison of the sequences of four cys promoters, a possible CysB-binding site was found which included the region shown to be required for the positive regulation of the cysJ promoter.