心脏多层CT数据中冠状动脉中轴的提取

提出一种冠状动脉跟踪算法,算法以局部血管模型为基础,采用三维几何矩、多尺度Hessian矩阵分析以及血管滤波算子,估计最优尺度下血管的中轴点坐标、尺寸及方向。算法采用跟踪策略以改进其效率,由初始种子点出发,依次提取冠状动脉血管的中轴点,最终构成冠状动脉血管树。分叉点检测算法能够有效地检测出可能的分叉点,并提取分支血管的种子点坐标。实验结果表明,算法能够有效地提取多层CT数据中的冠状动脉中轴线。结合估计的血管尺寸,三维模型能清楚地显示冠状动脉的解剖结构。同时算法有较高的计算效率,在普通的PC平台上,其运行时间能够控制在数分钟内。     

Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9

The low-density lipoprotein receptor (LDLR) prevents hypercholesterolemia and atherosclerosis by removing low-density lipoprotein (LDL) from circulation. Mutations in the genes encoding either LDLR or its ligand (APOB) cause severe hypercholesterolemia. Missense mutations in PCSK9, encoding a serine protease in the secretory pathway, also cause hypercholesterolemia. These mutations are probably gain-of-function mutations, as overexpression of PCSK9 in the liver of mice produces hypercholesterolemia by reducing LDLR number. To test whether loss-of-function mutations in PCSK9 have the opposite effect, we sequenced the coding region of PCSK9 in 128 subjects (50% African American) with low plasma levels of LDL and found two nonsense mutations (Y142X and C679X). These mutations were common in African Americans (combined frequency, 2%) but rare in European Americans (<0.1%) and were associated with a 40% reduction in plasma levels of LDL cholesterol. These data indicate that common sequence variations have large effects on plasma cholesterol levels in selected populations.     

The structure of theAspidosperma alkaloid compactinervine

Zusammenfassung Es wird über die Isolierung eines neuen Alkaloids — Compactinervin — aus der brasilianischen Apocynaceen-ArtAspidosperma compactinervium Kuhlm. berichtet. Durch massenspektroskopische und Kernresonanz-Messungen und chemische Umwandlungen konnte gezeigt werden, dass es sich beim Compactinervin um 19,20-Dihydroxy-19,20-dihydro-akuammicin handelt. Seine vollständige Stereochemie sowie die des verwandten Alkaloids Lochneridin konnte abgeleitet werden. Compactinervin stellt die erste Verbindung vom Akuammicin-Typ dar, die aus einerAspidosperma-Art isoliert worden ist.

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Paper XLI in the seriesAlkaloid Studies. For paper XL seeB. Gilbert, J. A. Brissolese, J. M. Wilson, H. Budzikiewicz, L. J. Durham, andC. Djerassi, Chem. and Ind.1962, 1949.

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Financial assistance in support of the joint research effort on Brazilian plants between Stanford University and the Instituto de Quimica Agricola was provided by the Rockefeller Foundation. Additional financial aid from the National Institutes of Health (grants AM 04257 and 2G-682) is gratefully acknowledged.     

Organic analysis of the Pueblito de Allende meteorite

It appears unlikely that the organic material detected in the meteorite that fell in Mexico last year can have been introduced by contamination.     

Primary cancer of the liver in rats after subcutaneous implantation of pellets of progesterone and testosterone propionate

Résumé Le carcinome hépatocellulaire du type trabéculaire a paru dans 2 rats sur 5, 745 jours après l'implantation de boulettes de progestérone cristallin et de propionate de testostérone, pesant 8 à 10 mg chacune. Un de ces rats a développé un carcinome provenant de l'épithélium d'une bronchiole respiratoire. L'absence d'une cholangiofibrosite antécédente, d'une nécrose ou d'une cirrhose hors de l'endroit de la tumeur du foie chez les rats soumis aux épreuves expérimentales, peut nécessiter un nouvel examen de la signification des lésions hépatiques comme facteur prédisposant au cancer chez l'homme.     

Essential role for the p110delta phosphoinositide 3-kinase in the allergic response

Inflammatory substances released by mast cells induce and maintain the allergic response. Mast cell differentiation and activation are regulated, respectively, by stem cell factor (SCF; also known as Kit ligand) and by allergen in complex with allergen-specific immunoglobulin E (IgE). Activated SCF receptors and high-affinity receptors for IgE (FcvarepsilonRI) engage phosphoinositide 3-kinases (PI(3)Ks) to generate intracellular lipid second messenger signals. Here, we report that genetic or pharmacological inactivation of the p110delta isoform of PI(3)K in mast cells leads to defective SCF-mediated in vitro proliferation, adhesion and migration, and to impaired allergen-IgE-induced degranulation and cytokine release. Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies.     

PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates

In addition to the apical-basal polarity pathway operating in epithelial cells, a planar cell polarity (PCP) pathway establishes polarity within the plane of epithelial tissues and is conserved from Drosophila to mammals. In Drosophila, a 'core' group of PCP genes including frizzled (fz), flamingo/starry night, dishevelled (dsh), Van Gogh/strabismus and prickle, function to regulate wing hair, bristle and ommatidial polarity. In vertebrates, the PCP pathway regulates convergent extension movements and neural tube closure, as well as the orientation of stereociliary bundles of sensory hair cells in the inner ear. Here we show that a mutation in the mouse protein tyrosine kinase 7 (PTK7) gene, which encodes an evolutionarily conserved transmembrane protein with tyrosine kinase homology, disrupts neural tube closure and stereociliary bundle orientation, and shows genetic interactions with a mutation in the mouse Van Gogh homologue vangl2. We also show that PTK7 is dynamically localized during hair cell polarization, and that the Xenopus homologue of PTK7 is required for neural convergent extension and neural tube closure. These results identify PTK7 as a novel regulator of PCP in vertebrates.     

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P < 0.0001). In transfection experiments, the transduction of growth hormone signaling through d3-GHR homo- or heterodimers was approximately 30% higher than through full-length GHR homodimers (P < 0.0001). One-half of Europeans are hetero- or homozygous with respect to the allele encoding the d3-GHR isoform, which is dominant over the full-length isoform. These observations suggest that the polymorphism in exon 3 of GHR is important in growth hormone pharmacogenetics.