Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture

BACKGROUND: Uterine leiomyomas (fibroids) are benign smooth muscle tumors that often contain an excessive extracellular matrix (ECM). In the present study, we investigated the interactions between human uterine leiomyoma (UtLM) cells and uterine leiomyoma-derived fibroblasts (FB), and their importance in cell growth and ECM protein production using a coculture system. RESULTS: We found enhanced cell proliferation, and elevated levels of ECM collagen type I and insulin-like growth factor-binding protein-3 after coculturing. There was also increased secretion of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor-2, and platelet derived growth factor A and B in the media of UtLM cells cocultured with FB. Protein arrays revealed increased phosphorylated receptor tyrosine kinases (RTKs) of the above growth factor ligands, and immunoblots showed elevated levels of the RTK downstream effector, phospho-mitogen activated protein kinase 44/42 in cocultured UtLM cells. There was also increased secretion of transforming growth factor-beta 1 and 3, and immunoprecipitated transforming growth factor-beta receptor I from cocultured UtLM cells showed elevated phosphoserine expression. The downstream effectors phospho-small mothers against decapentaplegic -2 and -3 protein (SMAD) levels were also increased in cocultured UtLM cells. However, none of the above effects were seen in normal myometrial cells cocultured with FB. The soluble factors released by tumor-derived fibroblasts and/or UtLM cells, and activation of the growth factor receptors and their pathways stimulated the proliferation of UtLM cells and enhanced the production of ECM proteins. CONCLUSIONS: These data support the importance of interactions between fibroid tumor cells and ECM fibroblasts in vivo, and the role of growth factors, and ECM proteins in the pathogenesis of uterine fibroids

Sub-surface mechanical damage distributions during grinding of fused silica

The distribution and characteristics of surface cracking (i.e. sub-surface damage or SSD) formed during standard grinding processes has been investigated on fused silica glass. The SSD distributions of the ground surfaces were determined by: (1) creating a shallow (18-108 {micro}m) wedge/taper on the surface by magneto-rheological finishing; (2) exposing the SSD by HF acid etching; and (3) performing image analysis of the observed cracks from optical micrographs taken along the surface taper. The observed surface cracks are characterized as near-surface lateral and deeper trailing indent type fractures (i.e., chatter marks). The SSD depth distributions are typically described by a single exponential distribution followed by an asymptotic cutoff in depth (c{sub max}). The length of the trailing indent is strongly correlated with a given process. Using established fracture indentation relationships, it is shown that only a small fraction of the abrasive particles are being mechanically loaded and causing fracture, and it is likely the larger particles in the abrasive particle size distribution that bear the higher loads. The SSD depth was observed to increase with load and with a small amount of larger contaminant particles. Using a simple brittle fracture model for grinding, the SSD depth distribution has been related to the SSD length distribution to gain insight into ''effective'' size distribution of particles participating in the fracture. Both the average crack length and the surface roughness were found to scale linearly with the maximum SSD depth (c{sub max}). These relationships can serve as useful rules-of-thumb for nondestructively estimating SSD depth and to identify the process that caused the SSD. In certain applications such as high intensity lasers, SSD on the glass optics can serve as a reservoir for minute amounts of impurities that absorb the high intensity laser light and lead to subsequent laser-induced surface damage. Hence a more scientific understanding of SSD formation can provide a means to establish recipes to fabricate SSD-free, laser damage resistant optical surfaces

Ampicillin/Sulbactam versus Cefuroxime as antimicrobial prophylaxis for cesarean delivery: a randomized study

<p>Abstract</p> <p>Background</p> <p>The efficacy and safety of a single dose of ampicillin/sulbactam compared to a single dose of cefuroxime at cord clamp for prevention of post-cesarean infectious morbidity has not been assessed.</p> <p>Methods</p> <p>Women scheduled for cesarean delivery were randomized to receive a single dose of either 3 g of ampicillin-sulbactam or 1.5 g of cefuroxime intravenously, after umbilical cord clamping. An evaluation for development of postoperative infections and risk factor analysis was performed.</p> <p>Results</p> <p>One hundred and seventy-six patients (median age 28 yrs, IQR: 24-32) were enrolled in the study during the period July 2004 - July 2005. Eighty-five (48.3%) received cefuroxime prophylaxis and 91 (51.7%) ampicillin/sulbactam. Postoperative infection developed in 5 of 86 (5.9%) patients that received cefuroxime compared to 8 of 91 (8.8%) patients that received ampicillin/sulbactam (p = 0.6). In univariate analyses 6 or more vaginal examinations prior to the operation (p = 0.004), membrane rupture for more than 6 hours (p = 0.08) and blood loss greater than 500 ml (p = 0.018) were associated with developing a postoperative surgical site infection (SSI). In logistic regression having 6 or more vaginal examinations was the most significant risk factor for a postoperative SSI (OR 6.8, 95% CI: 1.4-33.4, p = 0.019). Regular prenatal follow-up was associated with a protective effect (OR 0.04, 95% CI: 0.005-0.36, p = 0.004).</p> <p>Conclusions</p> <p>Ampicillin/sulbactam was as safe and effective as cefuroxime when administered for the prevention of infections following cesarean delivery.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier: NCT01138852</p

Stage-variations of anandamide hydrolase activity in the mouse uterus during the natural oestrus cycle

Recent studies have demonstrated that the endogenous cannabinoids are important modulators of fertility in mammals. In particular, a role of the endocannabinoid system in early stages of embryo development, oviductal transport of embryos, pregnancy maintenance and labour has been demonstrated in rodents and/or in humans. In the present paper, we report the analysis of FAAH activity and protein content in the mouse uterus as a function of the natural oestrus cycle stages. Variations of FAAH activity are discussed in relationship to changes in sex steroid levels and to the possible action of AEA on remodelling of uterine tissues

A programmable beam shaping system for tailoring the profile of high fluence laser beams

Customized spatial light modulators have been designed and fabricated for use as precision beam shaping devices in fusion class laser systems. By inserting this device in a low-fluence relay plane upstream of the amplifier chain, 'blocker' obscurations can be programmed into the beam profile to shadow small isolated flaws on downstream optical components that might otherwise limit the system operating energy. In this two stage system, 1920 x 1080 bitmap images are first imprinted on incoherent, 470 nm address beams via pixilated liquid crystal on silicon (LCoS) modulators. To realize defined masking functions with smooth apodized shapes and no pixelization artifacts, address beam images are projected onto custom fabricated optically-addressable light valves. Each valve consists of a large, single pixel liquid cell in series with a photoconductive Bismuth silicon Oxide (BSO) crystal. The BSO crystal enables bright and dark regions of the address image to locally control the voltage supplied to the liquid crystal layer which in turn modulates the amplitude of the coherent beams at 1053 nm. Valves as large as 24 mm x 36 mm have been fabricated with low wavefront distortion (&lt;0.5 waves) and antireflection coatings for high transmission (&gt;90%) and etalon suppression to avoid spectral and temporal ripple. This device in combination with a flaw inspection system and optic registration strategy represents a new approach for extending the operational lifetime of high fluence laser optics

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Programmable beam spatial shaping system for the National Ignition Facility

A system of customized spatial light modulators has been installed onto the front end of the laser system at the National Ignition Facility (NIF). The devices are capable of shaping the beam profile at a low-fluence relay plane upstream of the amplifier chain. Their primary function is to introduce 'blocker' obscurations at programmed locations within the beam profile. These obscurations are positioned to shadow small, isolated flaws on downstream optical components that might otherwise limit the system operating energy. The modulators were designed to enable a drop-in retrofit of each of the 48 existing Pre Amplifier Modules (PAMs) without compromising their original performance specifications. This was accomplished by use of transmissive Optically Addressable Light Valves (OALV) based on a Bismuth Silicon Oxide photoconductive layer in series with a twisted nematic liquid crystal (LC) layer. These Programmable Spatial Shaper packages in combination with a flaw inspection system and optic registration strategy have provided a robust approach for extending the operational lifetime of high fluence laser optics on NIF