Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.      

Familiäre systemisierte enchondrale Dysostose bei 3 Geschwistern

Zusammenfassung Es wird über eine Geschwistererkrankung aus der Gruppe der Dysostosis enchondralis berichtet. Die erhobenen klinischen, röntgenologischen und histologisch-pathologischen Befunde lassen eine Einordnung in die bisher bekannten Krankheitsformen nicht zu. Es handelt sich um einen Sonderfall einer systemisierten epi- und metaphysären Verknöcherungstörung der Röhrenknochen bei Neugeborenen, die innerhalb der ersten Lebenstage infolge schwerer generalisierter Krämpfe ad exitum kamen. Die beschriebenen Befunde lassen zwischen den Fällen lediglich graduelle Unterschiede erkennen. Obwohl es sich nach allerdings nicht ausreichender Sippenforschung um ein isoliertes Vorkommen dieser Erkrankungsform handelt, erscheint ein monogen-dominanter Erbgang mit unvoll-ständiger Penetranz am wahrscheinlichsten. Der Vererbungsmechanismus wird ebenso wie das allgemein gültige klinische Ordnungsprinzip dieser Erkrankung diskutiert.     

The pelvic digit ��eleventh finger��

Described as asymptomatic and an incidental finding on a plain x-ray film, the “pelvic digit” is a rare congenital anomaly. A 35-year-old man is of a rare symptomatic pelvic digit that warranted surgical excision. Its importance lies in its differentiation from acquired abnormalities due to trauma such as myositis ossificans and avulsion injuries of pelvis. If this entity is kept in mind, unnecessary investigations or interventions can be avoided.