Role of prostaglandin E 2 in cholinergic-mediated glycoprotein synthesis in canine antrum

We studied the mechanism of cholinergic stimulation of mucin synthesis in canine antral explants, including the role of PGE 2 as an intermediate messenger. Isolated antral mucosa was incubated with 10 −5 M carbachol (Cb), 10 −5 M indomethacin (IND), 10 −5 M pirenzepine (PZ), 10 −5 M Cb+10 −5 M PZ, 10 −5 M Cb+10 −5 M IND, and 10 −5 M IND +PGE 2 (10 −8 , 10 −7 and 10 −6 M) in the presence or absence of [ 3 H]glucosamine. After 24 hr, total glycoprotein synthesis was quantitated by Sepharose-4B chromatography and by 10% TCA/1%PTA precipitation with lipid extraction. PGE 2 released into the media was measured by radioimmunoassay (RIA). Cb significantly increased total glycoprotein synthesis and produced a significant increase in PGE 2 release. The increase in glycoprotein synthesis and the release of PGE 2 was blocked by the addition of muscarinic antagonist PZ. The addition of IND significantly inhibited glycoprotein synthesis and almost entirely suppressed PGE 2 secretion. IND also inhibited the effect of Cb on glycoprotein synthesis and PGE 2 release. Moreover, PGE 2 (10 −6 and 10 −7 M) significantly increased the glycoprotein synthesis in the canine stomach. This suggests the coordinate participation of PGE 2 -releasing cell population in modulation of glycoprotein synthesis in gastric mucosa.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44416/1/10620_2005_Article_BF01300285.pd

Prospecting in ultracool dwarfs : Measuring the metallicities of mid- and late-m dwarfs

© 2014. The American Astronomical Society. All rights reserved.Metallicity is a fundamental parameter that contributes to the physical characteristics of a star. The low temperatures and complex molecules present in M dwarf atmospheres make it difficult to measure their metallicities using techniques that have been commonly used for Sun-like stars. Although there has been significant progress in developing empirical methods to measure M dwarf metallicities over the last few years, these techniques have been developed primarily for early- to mid-M dwarfs. We present a method to measure the metallicity of mid- to late-M dwarfs from moderate resolution (R ∼ 2000) K-band (≃ 2.2 μm) spectra. We calibrate our formula using 44 wide binaries containing an F, G, K, or early-M primary of known metallicity and a mid- to late-M dwarf companion. We show that similar features and techniques used for early-M dwarfs are still effective for late-M dwarfs. Our revised calibration is accurate to ∼0.07 dex for M4.5-M9.5 dwarfs with -0.58 <[Fe/H] <+0.56 and shows no systematic trends with spectral type, metallicity, or the method used to determine the primary star metallicity. We show that our method gives consistent metallicities for the components of M+M wide binaries. We verify that our new formula works for unresolved binaries by combining spectra of single stars. Lastly, we show that our calibration gives consistent metallicities with the Mann et al. study for overlapping (M4-M5) stars, establishing that the two calibrations can be used in combination to determine metallicities across the entire M dwarf sequence.Peer reviewe

Extreme Asymmetry in the Disk of V1247 Ori

We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of ~0.14"-0.86" (54-330 au) from the central star. The polarized intensity (PI) image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.28" $\pm$ 0.09" in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at $\lesssim$46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.Comment: 21 pages, 5 figures, accepted for publication in PAS

Extreme Asymmetry in the Polarized Disk of V1247 Orionis *

We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of 0.′′14–0.′′86 (54–330 au) from the central star. The polarized intensity (PI) image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.′′28 0.′′09 in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at < 46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.This work is supported by MEXT KAKENHI Nos. 23103005. S.K. acknowledges support from an STFC Ernest Rutherford Fellowship (ST/J004030/1) and Marie Curie CIG grant (SH-06192)

Effect of sucralfate on components of mucosal barrier produced by cultured canine epithelial cells in vitro

The mucous gel maintains a neutral microclimate at the epithelial cell surface, which may play a role in both the prevention of gastroduodenal injury and the provision of an environment essential for epithelial restitution and regeneration after injury. Enhancement of the components of the mucous barrier by sucralfate may explain its therapeutic efficacy for upper gastrointestinal tract protection, repai, and healing. We studied the effect of sucralfate and its major soluble component, sucrose octasulfate (SOS), on the synthesis and release of gastric mucin and surface active phospholipid, utilizing an isolated canine gastric mucous cells in culture. We correlated these results with the effect of the agents on mucin synthesis and secretion utilizing explants of canine fundus in vitro . Sucralfate and SOS significantly stimulated phospholipid secretion by isolated canine mucous cells in culture (123% and 112% of control, respectively.) Indomethacin pretreatment siginificantly inhibited the effect of sucralfate, but not SOS, on the stimulation of phospholipid release. Administration of either sucralfate or SOS to the isolated canine mucous cells had no effect upon mucin synthesis or secretion using a sensitive immunoassay. Sucralfate and SOS did not stimulate mucin release in the canine explants; sucralfate significantly stimulated the synthesis of mucin, but only to 108% of that observed in untreated explants. No increase in PGE 2 release was observed after sucralfate or SOS exposure to the isolated canine mucous cells. Our results suggest sucralfate affects the mucus barrier largely in a qualitative manner. No increase in mucin secretion or major effect on synthesis was notd, although a significant increase in surface active phospholipid release was observed. The lack of dose dependency of this effect, along with the results of the PGE 2 assay, suggests the drug may act through a non-receptor-mediated mechanism to perturb the cell membrane and release surface active phospholipid. The enhancement of phospholipid release by sucralfate to augment the barrier function of gastric mucus may, in concert with other effects of the drug, strrengthen mucosal barrier function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44415/1/10620_2005_Article_BF01308079.pd

A method for the isolation of human gastric mucous epithelial cells for primary cell culture: A comparison of biopsy vs surgical tissue

We have developed a method for the isolation and growth of normal human gastric mucous epithelial cells using biopsies or surgically resected tissues as the source of the cells. The attachment and growth of cells were dependent upon: (1) cell planting density, ∼50,000 cells/cm 2 ; (2) extracellular matrix (fibronectin); and (3) and the use of a porous filter. In all experiments we found better cells attachment and growth of human gastric mucous cells isolated from surgical specimens compared with those gastric mucous cells isolated from gastric biopsies. The initial cell viability (as measured by Trypan-blue) was the same in both populations of gastric mucous epithelial cells isolated from either gastric biopsies or surgical specimens. After 4–5 days in culture one could detect various amounts of mucin in all the cells using either periodic acid Schiff (PAS) staining or a specific anti-mucin antibody. A similar pattern of much straining was also found in primary cultures of guinea pig gastric mucous epithelial cells. Immunohistochemical staining for chief cells (anti-pepsinogen) or parietal cells (anti-H + /K + ATPasc) in the gastric mucous cuboidal-like epithelial cells with tight junctions, desmosomes,short microvilli, a filamentous terminal web, mucous granules, and basal lamina-like structure. We could not detect the presence of fibroblasts during the 7–9 days that the primary cells were in culture. This cell culture method will prove useful in the isolation of normal human gastric mucous epithelial cells for in vitro studies of gastric mucosal injury and repair.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43235/1/11022_2004_Article_BF00127904.pd

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders