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Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes.  相似文献   
3.
Summary The degree of satellite association was found to be significantly higher in phytohemagglutinin (PHA)-stimulated lymphocytes from cystic fibrosis (CF) patients than from those of control individuals. PHA-stimulated lymphocytes from obligatory heterozygotes for the CF mutant allele showed an intermediate degree of satellite association. The degree of satellite association was estimated by the frequency of cells exhibiting associations, by the number of associations per cell, and by the number of chromosomes in an association. The differences in the degree of satellite association were dependent on the concentration of colchicine used for cell arrest. These findings may assist in developing a diagnostic method for the early identification of heterozygotes for the CF allele and for prenatal detection of CF homozygous fetuses.This paper is based on a portion of a dissertation to be submitted by Y. Ravia in partial fulfilment of the Ph. D. requirements in the Graduate School of Tel Aviv University  相似文献   
4.
Summary An analysis was made of the effects of different sampling and extraction techniques on the amounts and pattern of monoterpenoids isolated from needles of Norway spruce. The following isolation and analysis procedure was finally adopted: liquid nitrogen-cooled needles were pulverized by a microdismembrator, extracted with pentane overnight at 2°–3°C and concentrated to a volume not less than 3 ml/g fresh weight on a Vigreux column. The crude extract was injected splitless (with solvent split) onto a cold programmed temperature vaporized (PTV) precolumn of a gas chromatograph and the vaporizable compounds heated to a capillary column. This method was tested for production of artefacts and quantitative extraction and applied to needles of eleven 80-year-old spruce trees.  相似文献   
5.
The systemic injection of kainic acid (KA) has been shown to destroy neurons in the hippocampus and to induce limbic-type seizure activity. However, little is known on the neurochemical events that are associated with this convulsant effect. In the present work we studied the spontaneous and the K+-stimulated release of labeled -aminobutyric acid (GABA), glutamate, serotonin and dopamine, in hippocampal slices of KA-treated rats, at the moment of clinical seizures (2 h) and 72 h later. At the onset of convulsions we found a 40–45% decrease in the K+-stimulated release of GABA. The release of the other neurotransmitters was not significantly affected by KA treatment. After 72 h GABA release was still reduced by 30–40%. It is concluded that the epileptogenic effect of KA in the hippocampus is probably related to a diminished inhibitory GABAergic neurotransmission.  相似文献   
6.
Hepatic coma was induced in rats chronically treated with CCl4, by means of a single injection of ammonium acetate. The activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), as well as the synaptosomal uptake and release of [3H]GABA, were measured in the following brain areas of the comatose rats: cortex, striatum, hypothalamus, hippocampus, midbrain and cerebellum. Hepatic coma was associated with a general decrease of GAD activity, whereas GABA-T activity was diminished only in the hypothalamus, striatum and midbrain. During hepatic coma, the K+-stimulated [3H]GABA release was notably diminished in the striatum and cerebellum, whereas a significant increase was observed in the hippocampus. [3H]GABA uptake increased in most regions after CCl4 treatment, independently of the presence of coma. The results indicate that GABAergic transmission seems to be decreased in most cerebral regions during hepatic coma.  相似文献   
7.
Summary Twelve cases of lissencephaly are reported. A high resolution chromosome study was performed on each in order to detect small chromosomal anomalies, undetectable with routine techniques. Only one case was shown to have an unbalanced karyotype with a microdeletion of the short arm of chromosome 17(del 17p). This child also had symptoms of the Miller-Dieker syndrome, consisting of lissencephaly, characteristic facies, pre- and post-natal growth retardation and other birth defects. As proposed by Dobyns, it seems justifiable to classify lissencephalies into four different groups, according to other clinical manifestations and results of chromosome studies.  相似文献   
8.
Abstract Four plasmids were constructed by associating Escherichia coli and yeast selection markers and replication origins to a structural gene coding for aminoglycoside phosphotransferase (APH(3')) controlled by different flanking sequences. We used the two bacterial genes of Tn5 (APH(3')II) and Tn903 (APH(3')I) as such and the chimeric pSVneo (APH(3')II) and pNOSneo (APH(3')II) constructs, functional in mammalian and plant cells, respectively. Yeast clones resistant to G418 were obtained with all plasmids except with that bearing the bacterial APH(3')II gene. The three plasmids harbouring the functional APH genes, however, conferred different levels of G418 resistance to yeast.  相似文献   
9.
We construct a theoretical model of the transition structure for the carboxylation reaction of ribulose-1,5-biphosphate catalyzed by Rubisco. This is a first-order saddle point on the energy hypersurface for the nucleophilic attack of carbon dioxide on CH3-(CHOH)3-CH3 at the C2 center.Ab initio analytical gradients methods at a 4-31G basis set level are used.The carbon framework and oxygens of the stationary structure superpose with the corresponding atoms of 2-carboxyarabinitol-1,5-biphosphate, which is a transition state analog that has recently been highly refined with X-ray methods. The hydroxyl group in C3 iscis to the C2 oxygen. The C3 center is somewhat pyramidized, the dienol O2-C2-C3-O3 is not planar.The geometry of the transition state allows for simple explanations of both the enolization of Rubisco's substrate ribulose-1,5-biphosphate, O3PO-CH2-CO-(CHOH)2-CH2-OPO3 and oxygenation reaction. The former is due to the pyramidal deformation at C3 and out of plane of O2-C2-C3-O3 framework: the enoliation is intramolecular and is probably enhanced by proton tunnelling. The latter is related with the fact that a rotation around an ethylene-like bond brings the triplet state down in energy. The reactive skeleton has a stationary geometry in the triplet state not very different from the one obtained in the global transition structure. There, the triplet is only 9 kcal/mol above the singlet. The spin densities at C2 and C3 centers clearly indicate the place where oxygenation will take place.  相似文献   
10.
The dependence of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) release on Ca2+ was comparatively studied in synaptosomes from mouse brain, by correlating the influx of 45Ca2+ with the release of the transmitters. It was observed that exposure of synaptosomes to a Na+-free medium notably increases Ca2+ entry, and this condition was used, in addition to K+ depolarization and the Ca2+ ionophore A23187, to stimulate the influx of Ca2+ and the release of labeled GABA and ACh. The effect of ruthenium red (RuR) on these parameters was also investigated. Of the three experimental conditions used, the absence of Na+ in the medium proved to be the most efficient in increasing Ca2+ entry. RuR inhibited by 60-70% the influx of Ca2+ stimulated by K+ depolarization but did not affect its basal influx or its influx stimulated by the absence of Na+ or by A23187. The release of ACh was stimulated by K+ depolarization, absence of Na+ in the medium, and A23187 in a strictly Ca2+-dependent manner, whereas the release of GABA was only partially dependent on the presence of Ca2+ in the medium. The extent of stimulation of ACh release was related to the extent of Ca2+ entry, whereas no such correlation was observed for GABA. In the presence of Na+, RuR did not affect the release of the transmitters induced by A23187. In the absence of Na+, paradoxically RuR notably enhanced the release of both ACh and GABA induced by A23187, in a Ca2+-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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