Ampicillin blood levels as related to graded oral schedules - Minimal effect of ampicillin-associated diarrhea upon drug absorption and other therapeutic considerations

Twenty children, while hospitalized with pneu monia, were treated by randomization with graded dosages of oral ampicillin; five each received 50, 100, 150, or 200 mg/kg daily in four equally divided doses for at least five days. The peak serum levels rose from a mean of 1 mcg/ml with 50 mg/kg per day to 4 to 7 mcg/ml with 200 mg/kg per day. Mild to moderate diarrhea, encountered in two of the five patients of each study group, was apparently unrelated to dose, and did not hinder absorption of the drug to a clinically significant degree

A Novel Transforming Growth Factor-β Receptor-interacting Protein That Is Also a Light Chain of the Motor Protein Dynein

The phosphorylated, activated cytoplasmic domains of the transforming growth factor-β (TGFβ) receptors were used as probes to screen an expression library that was prepared from a highly TGFβ-responsive intestinal epithelial cell line. One of the TGFβ receptor-interacting proteins isolated was identified to be the mammalian homologue of the LC7 family (mLC7) of dynein light chains (DLCs). This 11-kDa cytoplasmic protein interacts with the TGFβ receptor complex intracellularly and is phosphorylated on serine residues after ligand-receptor engagement. Forced expression of mLC7-1 induces specific TGFβ responses, including an activation of Jun N-terminal kinase (JNK), a phosphorylation of c-Jun, and an inhibition of cell growth. Furthermore, TGFβ induces the recruitment of mLC7-1 to the intermediate chain of dynein. A kinase-deficient form of TGFβ RII prevents both mLC7-1 phosphorylation and interaction with the dynein intermediate chain (DIC). This is the first demonstration of a link between cytoplasmic dynein and a natural growth inhibitory cytokine. Furthermore, our results suggest that TGFβ pathway components may use a motor protein light chain as a receptor for the recruitment and transport of specific cargo along microtublules