Glycosaminoglycans (GAGs), especially heparan sulfate, are involved in the anticoagulant property of vascular endothelium. It was observed that heparin-like activity on the surface of cultured bovine aortic endothelial cells was enhanced by cadmium at 1.0 microM or more after a 24-h incubation. The incorporation of [3H]glucosamine into GAGs, a marker of GAG synthesis, was markedly increased by cadmium at 0.5 microM or more in both the cell layer and the conditioned medium; however, the incorporation of [35S]sulfate, a marker of the GAG sulfation, was significantly reduced by the metal at 2.0 microM or more. Similar changes were observed in a cultured human umbilical vein endothelial cell layer. Characterization of GAGs in bovine endothelial cell layer revealed that cadmium (2.0 microM)-induced alterations mostly occurred in the major component heparan sulfate rather than in other minor GAGs. Stimulation of [3H]glucosamine incorporation by cadmium at 2.0 microM occurred even in the presence of p-nitrophenyl-beta-D-xyloside but disappeared in the presence of cycloheximide, suggesting that cadmium might induce the production of proteins which are involved in GAG synthesis. The present data suggest that vascular endothelial cells are capable of enhancing the potential anticoagulant activity on their surface via induction of heparan sulfate synthesis. This response of endothelial cells may be a defensive one to the procoagulant state of blood which can be induced by cadmium.

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PubMedDate not supplied

Innovative culture shock prescribed for health care.

Finally, organizations must accept that inefficiencies are often present in creative cultures. Resources that were devoted to operating and revenue-generating functions must be shifted to finance the capacity to be creative. The short-term focus of today's organizations blinds them from envisioning the long-term benefits of fostering creative changes and improvements. When creativity is properly managed, meaningful risks may be taken with reasonable costs occasionally yielding monumental results.

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PubMedDate not supplied

Cycloprodigiosin hydrochloride, a H+/Cl- symporter, induces apoptosis in human colon cancer cell lines in vitro.

Recently, we reported that cycloprodigiosin hydrochloride (cPrG.HCl), a novel H+/Cl- symporter, induces acidification of the cytosol and leads to apoptosis on rat and human liver cancer cells. In the present study, the effects of cPrG.HCl, a H+/Cl- symporter, were examined in colon cancer cell lines in vitro. In the MTT assay, cPrG.HCl inhibited the growth of two colon cancer cell lines (WiDr and SW480) in a dose- and time-dependent manner. The cPrG.HCl treatment of both types of cells induced apoptosis as confirmed by the appearance of a sub-G1 population and intranucleosomal DNA fragmentation. In addition, cPrG.HCl lowered pHi (below pH 6.8) respectively. Therefore, these results suggest that cPrG.HCl may be useful for the treatment of colon cancer cells.

Antiporters↗

PubMedDate not supplied

Mechanism of long-term potentiation in the hippocampus--a quantal analysis study.

We addressed a question as to whether long-term potentiation (LTP) results from an increase in amount of neurotransmitter liberated in response to presynaptic impulses or from an elevated responsiveness of postsynaptic neurons to the neurotransmitter. As a model of LTP, we took a potentiation of synaptic transmission by phorbol diacetate, and applied quantal analysis. Unitary excitatory postsynaptic potentials (EPSPs) were induced in CA3 neurons by activation of single granule cells in thin transverse sections of the hippocampus of the guinea pig. A series of EPSPs was recorded before and during administration of phorbol diacetate at 100-450 nM, the amplitude of all recorded EPSPs was measured, and the values of mean quantal amplitude (q) and mean quantal content (m) were calculated by variance method. In control solution, the values of m and q were 9.7 and 1.1 mV, respectively. Potentiation of synaptic transmission by phorbol diacetate was accompanied by increases in the value of m. The value of q remained unchanged in most neurons and decreased in some. These results indicate that the phorbol ester causes an increase in release of transmitter and thereby potentiates transmission through synapses between mossy fibers and CA3 neurons.

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