Faculty Bibliography

Presents a short story entitled Ma, A Memoir (L. Freed, 1996) to illustrate some of the characteristics of dementia to aid medical students and other inexperienced health care workers in distinguishing a patient's dementia from willful or perverse behavior. The story may elicit quite human reactions to senile behavior and evoke a discussion that is useful for developing self-knowledge and understanding required of a health care professional.

A major aim of this investigation was to determine whether, in steady-state ascites cells, Cl- transport can be partitioned into a furosemide-sensitive cotransport with K+ and a separate 4,4'-isothiocyanostilbene-2,2'-disulfonic acid (DIDS) sensitive self-exchange. Both Cl- and K+ fluxes were studied. The furosemide- and Cl- sensitive K+ fluxes were equivalent, both in normal ionic media and when the external K+ concentration, [K+]o, was varied from 4 to 30 mM. The stoichiometry of the furosemide-sensitive Cl- and K+ fluxes was 2 Cl-:1 K+ at 0.1 and 0.5 mM drug levels but increased to 3 Cl-:1 K+ at 1.0 mM furosemide. DIDS at 0.1 mM had no effect on the K+ exchange rate but inhibited Cl- exchange by 39% +/- 2 (S.E.). The effects of DIDS and 0.5 mM furosemide on Cl- transport were additive but 1.0 mM furosemide and DIDS had overlapping inhibitory actions. Thus furosemide acts on components of K+ and Cl- transport which are linked to each other, but the drug also inhibits an additional DIDS-sensitive Cl- pathway, when present at higher concentrations. The dependence of the furosemide-sensitive K+ and Cl- transport on [K+]o was also studied; both fluxes fell as the [K+]o increased. The latter results recall those in an earlier study by Hempling (Hempling, H.G. (1962) J. Cell. Comp. Physiol. 60, 181-198)

Bumetanide is a potent diuretic drug which has some structural features in common with furosemide. The steady-state exchange of K+ and Cl- was investigated in Ehrlich ascites tumor cells treated with bumetanide. This agent did not alter the cellular content of K+ or Cl- but the self-exchange of both ions was depressed. K+ self-exchange was inhibited by 55% at bumetanide concentrations as low as 10(-6) M. Cl- self-exchange was less sensitive to this drug but at low concentrations (between 10(-6) and 10(-3) M) bumetanide was a more effective inhibitor of Cl- transfer than furosemide. The steady-state K+ flux of cells equilibrated in NO3- media was compared with the K+ flux in cells treated with 10(-4) or 10(-3) M bumetanide; the Cl(-)-sensitive K+ exchange was equivalent to the bumetanide-sensitive K+ exchange. Since the results suggested that a bumetanide-sensitive (Cl-, K+) cotransport could be operative in steady-state cells, the stoichiometry of the bumetanide-sensitive fluxes was determined by measuring Cl- and K+ fluxes simultaneously in the same cell suspension. At 5 . 10(-4) and 10(-3) M bumetanide concentrations, the ratio of these fluxes was 0.98 +/- 0.07 (S.E.) and 1.04 +/- 0.06, respectively, consistent with the postulated cotransport mechanism. At 10(-4) and 10(-5) M, however, the ratio of the bumetanide-sensitive Cl-/K+ flux was significantly less than 1.0. Since the magnitude of the bumetanide-sensitive K+ flux at 10(-4) M was close to that of the Cl(-)-sensitive flux, a ratio of less than 1.0 at this drug level indicates that Cl-sensitivity and drug sensitivity may not reflect inhibition of the same process under all circumstances

The effects of 1-isothiocyanate-4-benzene sulfonic acid on steady state Cl- and SO24(4 transport in Ehrlich mouse ascites tumor cells were investigated. At 10 mM, 1-isothiocyanate-4-benzenesulfonic acid reduced SO24(-) exchange by 94% but Cl- exchange was reduced by only 37%; Cl- exchange was not further inhibited by as much as 60 min of preincubation with 1-isothiocyanate-4-benzenesulfonic acid. Inhibition of Cl- exchange was completely reversible following 30-45 min of contact with 1-isothiocyanate-4-benzenesulfonic acid whereas under the same conditions, inhibition of SO24(-) exchange was irreversible. The effect o 1-isothiocyanate-4-benzenesulfonic acid on SO24(-) transport could be reversed, however, when exposure to 1-isothiocyanate-4-benzene-sulfonic acid lasted for only 2 min. In these respects the action of 1-isothiocyanate-4-benzenesulfonic acid resembles that of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonic acid; the results are compatible with separate membrane sites for Cl- and SO24(-) transport. The Ki for reversible inhibition of SO24(-) transport, determined from a Dixon plot, was 4.8 mM and the inhibition appeared to be non-competitive