Load compensation in obese patients during quiet tidal breathing

Seventeen eucapnic massively obese patients and eight normal subjects had their respiratory cycle parameters studied while breathing room air at rest. Despite large variations in the degree of obesity, our patients demonstrated normal mean inspiratory and expiratory flow rates, duty cycles, and minute ventilation. The maintenance of normal mean inspiratory flow rates was found to be dependent on an augmentation of neuromuscular drive (P0.1); furthermore, a strong positive correlation between percentage ideal body weight (i.e., the degree of obesity) and P0.1 was present. The obese were found to partition their tidal volume preferentially to their rib cage compartment, choosing to leave the abdominal compartment relatively immobile. Analysis of the diaphragmatic electromyogram revealed a persistence of activity into early expiration, the length of which also depended on the degree of obesity. These findings suggest that the diaphragm's volume-generating function in the obese is reduced, and furthermore the persistence of its activity in expiration serves to attenuate the rate of expiratory flow. No significant difference in any respiratory cycle parameter was found between simple obesity patients and formerly hypercapnic obese patients.     

The effect of sphingosine and phorbol ester on the signal transduction enzymes and fibronectin release in cell culture.

In testing the hypothesis that the stimulation of the release of fibronectin (FN) by 12-O-tetradecanoylphorbol 13-acetate (TPA) from human lung fibroblasts in culture is the result of activation of protein kinase C (PKC), we found that the PKC inhibitor sphingosine strongly inhibited FN release in presence and even in absence of TPA. However, a different PKC inhibitor, calphostin C, despite almost complete inhibition of PKC, had no effect on FN release. We concluded that sphingosine is a potent inhibitor of FN release from the cell surface, independent of its inhibition of PKC; and that TPA stimulates release of FN by a pathway other than activation of PKC. We found that the activation of PKC by TPA was accompanied by inhibition of the cAMP-dependent protein kinase (PKA). When PKA was inhibited by an antagonist (H8, a cAMP analogue) at a concentration specific for PKA inhibition, the release of FN was stimulated similar to the stimulation with TPA. Activation of PKA with forskolin resulted in decreased FN release. In conclusion, we have shown that: (1) sphingosine had a robust effect inhibiting the release of FN from fibroblasts, independent of its action on PKC; (2) TPA treatment of these cells resulted in inhibition of PKA; (3) inhibition of PKA stimulated FN release whereas its activation decreased this release. It is possible that PKA, by phosphorylating a protein, may function, directly or indirectly, in keeping FN attached to the cell surface of fibroblasts.