Pro- and anti-inflammatory cytokines in threatened miscarriages

OBJECTIVE: The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatenedmiscarriage (TM) and subsequent outcome. STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF , interferon gamma (IFN ), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS: Monocyte expression of TNF and circulating levels of TNF , IFN , IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF /IL-10, IFN /IL-10, and TNF /IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome. CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage.peer-reviewe

Investigation of systemic inflammatory response in first trimester pregnancy failure

Background: The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage. Methods: Levels of tumour necrosis factor alpha (TNFa), TNF receptors 1 and 2, interferon gamma (IFNg), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW. Results: The plasma of women with euploid miscarriage contained significantly higher circulating levels of TNFa (P , 0.005), IFNg (P , 0.005), IL-6 (P , 0.005) and IL-10 (P , 0.01) than that of pregnant controls, irrespective of gestational age. Significantly (P , 0.05) higher TNF-R1 levels at 6–9 weeks, and significantly higher TNFa/IL-6 (P , 0.001) and significantly lower TNFa/IL-10 (P , 0.001) and IFNg/IL-10 (P , 0.001) ratios at 10–14 weeks, were also found in euploid miscarriage cases compared with pregnant controls. TNFa/IL-10 ratio in plasma was significantly (P , 0.05) lower in miscarriages with an abnormal karyotype than those with normal karyotype. Normal pregnant women had a significantly higher plasma level of IFNg (P , 0.01) and IFNg/IL-10 ratio (P , 0.005), a significantly (P , 0.005) lower TNF-R1 level, and a significant (P , 0.05) increase in stimulated TNFa in monocytes, compared with NPW. Conclusions: Our data confirm that there is an inflammatory reaction in normal pregnancy compared with the non-pregnant state, which may be disrupted during miscarriage.peer-reviewe

Pro-and antiinflammatory cytokines in threatened miscarriages

OBJECTIVE: The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatened miscarriage (TM) and subsequent outcome. STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF␣, interferon gamma (IFN␥), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS: Monocyte expression of TNF␣ and circulating levels of TNF␣, IFN␥, IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF␣/IL-10, IFN␥/IL-10, and TNF␣/IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome. CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage

The Solar Activity Monitor Network – SAMNet

The Solar Activity Magnetic Monitor (SAMM) Network (SAMNet) is a future UK-led international network of ground-based solar telescope stations. SAMNet, at its full capacity, will continuously monitor the Sun’s intensity, magnetic, and Doppler velocity fields at multiple heights in the solar atmosphere (from photosphere to upper chromosphere). Each SAMM sentinel will be equipped with a cluster of identical telescopes each with a different magneto-optical filter (MOFs) to take observations in K I, Na D, and Ca I spectral bands. A subset of SAMM stations will have white-light coronagraphs and emission line coronal spectropolarimeters. The objectives of SAMNet are to provide observational data for space weather research and forecast. The goal is to achieve an operationally sufficient lead time of e.g., flare warning of 2–8 h and provide many sought-after continuous synoptic maps (e.g., LoS magnetic and velocity fields, intensity) of the lower solar atmosphere with a spatial resolution limited only by seeing or diffraction limit, and with a cadence of 10 min. The individual SAMM sentinels will be connected to their master HQ hub where data received from all the slave stations will be automatically processed and flare warning issued up to 26 h in advance

KSHV Manipulates Notch Signaling by DLL4 and JAG1 to Alter Cell Cycle Genes in Lymphatic Endothelia

Increased expression of Notch signaling pathway components is observed in Kaposi sarcoma (KS), but the mechanism underlying the manipulation of the canonical Notch pathway by the causative agent of KS, Kaposi sarcoma herpesvirus (KSHV), has not been fully elucidated. Here, we describe the mechanism through which KSHV directly modulates the expression of the Notch ligands JAG1 and DLL4 in lymphatic endothelial cells. Expression of KSHV-encoded vFLIP induces JAG1 through an NF kappa B-dependent mechanism, while vGPCR upregulates DLL4 through a mechanism dependent on ERK. Both vFLIP and vGPCR instigate functional Notch signalling through NOTCH4. Gene expression profiling showed that JAG1- or DLL4-stimulated signaling results in the suppression of genes associated with the cell cycle in adjacent lymphatic endothelial cells, indicating a role for Notch signaling in inducing cellular quiescence in these cells. Upregulation of JAG1 and DLL4 by KSHV could therefore alter the expression of cell cycle components in neighbouring uninfected cells during latent and lytic phases of viral infection, influencing cellular quiescence and plasticity. In addition, differences in signaling potency between these ligands suggest a possible complementary role for JAG1 and DLL4 in the context of KS

Degranulation of individual mast cells in response to Ca 2� and guanine nucleotides: an all-or-none event

Abstract. Widespread experience indicates that application of suboptimal concentrations of stimulating ligands (secretagogues) to secretory cells elicits submaximal extents of secretion. Similarly, for permeabilized secretory cells, the extent of secretion is related to the concentration of applied intracellular effectors. We investigated the relationship between the extent of secretion from mast cells (assessed as the release of hexosaminidase) and the degranulation (exocytosis) responses of individual cells. For permeabilized mast cells stimulated by the effector combination Ca 2+ plus GTP-3,-S and for intact cells stimulated by the Ca 2÷ ionophore ionomycin, we found that exocytosis has the characteristics of an all-or-none process at the level of the individual cell. With a suboptimal stimulus, th

Evaluation of platform using a bioluminescent protein.

<p>Bacteria were transformed with the screening vector containing either the firefly luciferase variant x5_FLuc (~550nm) or a red-shifted variant of firefly luciferase x5_Fluc_red (~615nm). An input sample, composed of x5_FLuc expressing bacteria with x5_Fluc_red expressing bacteria spiked in at 0.5%, was printed using the screening platform. a) Bioluminescent images of the plates were then acquired using PhotonIMAGER^™Optima (<i>Biospace lab</i>) through 6 bandpass filters ranging from 510-750nm. Images shown represent sections of a plate acquired through a 550-600nm bandpass filter and a 590-640nm bandpass filter, the same red shifted FLuc colony is highlighted in both images. Images were then analysed using CellProfiler software, giving an intensity value for each individual colony through each of the 6 filters to give a 6-point bioluminescent emission spectrum. b) Shows the spectrum for an x5_Fluc colony and c) shows the spectrum for an x5_Fluc_red colony. d) Finally, a x5_Fluc colony and a x5_FLuc_red colony were picked and a bioluminescent emission spectrum was taken using crude bacterial lysates using a multimodal plate reader (10nm intervals between 500-750nm) to confirm the bioluminescent emission spectrum produced through the screening platform.</p

Comparison of conventional electromechanical target translation vs sort stream multiplexing.

<p>a) The conventional methodology predicates that the target is physically moved to the next position before the machine can deposit a particle which incurs a cumulative time penalty. With electrostatic stream translation, the target remains stationary during each burst. b) Image demonstrating the 9 streams produced by the electronic sorter when using the multiplexer device. c) A bioluminescent image of a bacterial plate deposited using the sort-multiplexing device. The bacteria were printed in high-speed bursts in groups of 9 to form this 4,050-point matrix.</p