Colorectal Cancers Mimic Structural Organization of Normal Colonic Crypts

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.     

Exclusion mapping of the X-linked dominant chondrodysplasia punctata/ichthyosis/cataract/short stature (Happle) syndrome: possible involvement of an unstable pre-mutation

Summary Homology with the mouse bare patches mutant suggests that the gene for the X-linked dominant chondrodysplasia punctata / ichthyosis / cataract / short stature syndrome (Happle syndrome) is located in the human Xq28 region. To test this hypothesis, we performed a linkage study in three families comprising a total of 12 informative meioses. Multiple recombinations appear to exclude the Xq28 region as the site of the gene. Surprisingly, multiple crossovers were also found with 26 other markers spread along the rest of the X chromosome. Two-point linkage analysis and analysis of recombination chromosomes seem to exclude the gene from the entire X chromosome. Three different mechanisms are discussed that could explain the apparent exclusion of an X-linked gene from the X chromosome by linkage analysis: (a) different mutations on the X chromosome disturbing X inactivation, (b) metabolic interference, i.e. allele incompatibility of an X-linked gene, and (c) an unstable pre-mutation that can become silent in males. We favour the last explanation, as it would account for the unexpected sex ratio (MF) of 1.21 among surviving siblings, and for the striking clinical variability of the phenotype, including stepwise increases in disease expression in successive generations.     

Electrorotation of lymphocytes—The influence of membrane events and nucleus

Electrorotation—the spin of cells in rotating high frequency electric fields—has been used to investigate properties of human peripheral blood lymphocytes. The rotation spectra of lymphocytes deviate from those of single shell spheres. The deviations are caused by the electrical properties of the nucleus in the cell interior.Electrorotation allows the distinction between successfully stimulated lymphocytes and unstimulated cells after application of concanavalin A. Notwithstanding the fact that only a proportion of the cells will be mitogenically stimulated we detected an enhanced cell membrane conductivity for the whole cell population immediately after the addition of mitogen.     

Elektronenmikroskopische Untersuchungen an der Reptilien- und Vogellunge

Zusammenfassung Elektronenmikroskopische Untersuchungen ergeben, daß nicht nur die respiratorische Oberfläche der Reptilienlunge, sondern auch der Lunge der Vögel jene Dreischichtung aufweist, wie sie für die Atmungsfläche der Amphibien und Säugerlunge bereits nachgewiesen wurde: Sie gliedert sich in Endothel, Basalmembran und einschichtiges Epithel. Allerdings liegen in der Vogellunge insofern besondere Verhältnisse vor, als das Cytoplasma der Deckzellen in den Luftkapillaren zu sehr dünnen Platten ausgezogen ist, die sich stellenweise ziemlich regelmäßig übereinander schichten und in den Nischen zwischen den Blutkapillaren auffällige Membrankonvolute bilden. Mit dieser Peststellung ergibt sich, daß weder die eingangs erwähnte, die Vogellunge betreffende Darstellung von Schulz (1959) noch jene von Salt und Zeuthen (1960) den tatsächlichen Verhältnissen gerecht wird.Die ältere Ansicht (Bargmann 1935, 1936), wonach die Vogellunge als ein intensiver Beatmung in höchstem Maße angepaßtes Organ am Ende einer funktioneilen Reihe steht, erweist sich zwar insofern als unzutreffend, als ihre Blutkapillaren nicht weitgehend nackt an die Atemluft angrenzen. Sie kann jedoch deswegen noch Geltung beanspruchen, weil die Cytoplasmaauskleidung ihrer Luftkapillaren auf große Strecken hin wesentlich dünner als die Epithelauskleidung der Lungenalveolen der Säugetiere ist.Durchgeführt mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft.Herrn Prof. Dr. Wilhelm Hallermann, Direktor des Instituts für Gerichtliche und Soziale Medizin an der Universität Kiel, zum 60. Geburtstag dankbar gewidmet.     

Uptake, transport and metabolism of cytokinin in moss protonema

Uptake, transport and metabolism of cytokinin in the protonemaof Funaria hygrometrica were studied using labelled kinetin(6-furfurylamino [8-¹⁴C]-purine). All cells of the protonema,chloronema and caulonema, were able to take up kinetin, whichwas carried in the symplastic transport system from cell tocell. Radioactivity was especially accumulated in growing cellsof the protonema. Kinetin was metabolized immediately afteruptake. While only very little kinetin (less than 1%) remainedas free kinetin and one part was immobilized in chromatographicseparation [e.g. attached to proteins and incorporated intonucleic acids (17)], most of the remaining kinetin was metabolizedto adenine derivatives. Exogenously supplied adenosine changedthe metabolism of kinetin. In the caulonema, adenosine reducedthe turnover of kinetin to other adenine derivatives and enhancedthe content of labelling in the start fraction. Thus adenosinecan stimulate cytokinin-dependent bud formation in moss protonema. (Received November 24, 1977; )     

Transparent Golgi Impregnations: A Way to Examine Both Details of Cellular Processes and Components of the Nerve Cell Body

A method is described by which the precipitate that normally fills impregnated cells in Golgi preparations is confined to a thin and transparent scattering of fine particles that defines the somata and cellular processes. The coating is stable enough to withstand counterstaining and thus makes possible direct evaluation of structural features not only of cellular processes but also of cytoplasmic components.     

In vitro attachment of Treponema hyodysenteriae to mammalian epithelial cells.

The interaction between Treponema hyodysenteriae and isolated swine intestinal epithelial cells or mouse adrenal cells in culture was examined. Studies were performed in which treponemes were incubated with each type of anomal cell in an atmosphere of 5% CO2 in air. Coincubation was terminated at various time intervals, and the percentage of treponemal attachment evaluated by light microscopy. The extent of attachment was dependent on both incubation time and temperature. The mechanism of attachment to the animal cell surface was examined by scanning electron microscopy. Interaction of the parasite with the host cell did not appear to alter cellular morphology or result in changes of the cell surface at the site of attachment. Preference for a cellular site of attachment was not found.