Doppler velocimetry of the umbilical artery as a predictor of outcome in pregnancies characterized by elevated beta-subunit human chorionic gonadotropin.

OBJECTIVE: Women with unexplained elevated maternal serum beta-subunit human chorionic gonadotropin (beta-HCG) are at an increased risk for adverse pregnancy outcome, most likely due to placental abnormalities. Such abnormalities may also result in disturbed blood flow through placental vessels. The purpose of this study was to assess whether Doppler velocimetry of the umbilical artery has a predictive value for pregnancy outcome in patients with unexplained elevated maternal serum beta-HCG. STUDY DESIGN: The study group included 63 patients, in whom the only finding was elevated maternal serum beta-HCG. Systolic/diastolic (S/D) ratios were calculated using a continuous wave Doppler measurement of the umbilical artery, performed beginning at 22 weeks of gestation and followed at 6- to 8-week intervals. Serial results for each individual were incorporated into a single 'velocimetry score', calculated as the rate of abnormal velocimetry measurements. RESULTS: beta-HCG was found to be associated with poor pregnancy outcome: including intrauterine growth restriction (IUGR) (19%), pregnancy-induced hypertension (PIH) (14%), and preterm labor (PTL) (19%). Patients were then divided into 2 groups according to their velocimetry score: group A, VS < or = 80 (n = 47), and group B, VS > 80 (n = 16). A low velocimetry score was associated with a higher rate of IUGR, PIH, and a significantly higher rate of PTL. CONCLUSIONS: Umbilical artery Doppler velocimetry may serve as a predictor of pregnancy outcome in the high-risk group characterized by unexplained elevated beta-HCG.

Active extrusion of potassium in the yeast Saccharomyces cerevisiae induced by low concentrations of trifluoperazine.

Trifluoperazine (TFP), the antipsychotic drug, induces substantial K+ efflux, membrane hyperpolarization and inhibition of H+-ATPase in the yeast Saccharomyces cerevisiae. Investigations on the mechanism of these effects revealed two different processes observed at different incubation conditions. At an acidic pH of 4.5 and an alkaline pH of 7.5, K+ efflux was accompanied by substantial proton influx which led to intracellular acidification and dissipation of delta psi formed by cation efflux. The results indicated nonspecific changes in membrane permeability. Similar results were also observed when cells were incubated at pH 5.5-6.0 with higher concentrations of TFP (above 75 microM). On the other hand, low concentrations of TFP (30-50 microM) at pH 5.5-6.0 caused marked membrane hyperpolarization and K+ efflux unaccompanied by the efflux of other cations and by H+ influx. Our experiments indicate that under these conditions K+ efflux was an active process. (1) K+ efflux proceeded only in the presence of a metabolic substrate and was inhibited by metabolic inhibitors. (2) When 0.3-0.9 mM-KCl was present in the medium at pH 6.0, the concentration of K+ within the cells (measured at the end of the incubation with TFP) was much lower than the theoretical concentration of Kin+ if the distribution of K+ between medium and cell water was at equilibrium (at zero electrochemical gradient). (3) Valinomycin decreased the net K+ efflux and decreased the membrane hyperpolarization induced by TFP, probably by increasing the flux of K+ into the cells along its electrochemical gradient. (4) Conditions which led to active K+ efflux also led to a marked decrease in cellular ATP level. The results indicate that under a specific set of conditions TFP induces translocation of K+ against its electrochemical gradient.

Mechanism of stimulation of Ca2+ uptake by miconazole and ethidium bromide in yeasts: role of vacuoles in Ca2+ detoxification.

The antifungal antibiotic miconazole and the cationic dye ethidium bromide, both caused K+ efflux, membrane depolarization and intracellular acidification in the yeast Saccharomyces cerevisiae. Whereas miconazole inhibited the activity of the plasma membrane H+-ATPase, no such inhibition was observed using ethidium bromide at concentrations up to 600 microM. Low concentrations of both drugs caused marked stimulation of the energy dependent Ca2+ uptake. The extra Ca2+ taken up in the presence of the drugs was localized within the vacuoles, whereas K+ was lost mainly from the cytosolic pool. The ions Zn2+ and La3+ inhibited the effect of both drugs on the stimulation of Ca2+ uptake. The results indicated that both drugs caused an increase in the permeability of cell membranes to ions, leading to an increase in the influx of Ca2+ into the cytosol along its electrochemical gradient. Consequently, the concentration of Ca2+ within the cytosol increased and in turn led to the enhancement of Ca2+ uptake by the energy dependent vacuolar Ca2+ system, which functioned as a Ca2+ detoxification system.

Effects of inhibitors of plasma-membrane ATPase on potassium and calcium fluxes, membrane potential and proton motive force in the yeast Saccharomyces cerevisiae.

The plasma membrane ATPase inhibitors N,N-dicyclohexylcarbodiimide (DCCD), diethylstilboestrol and sodium orthovanadate caused inhibition of proton ejection in Saccharomyces cerevisiae at a concentration range of 0.1-0.4 mM. At this concentration K+ efflux was not observed; DCCD caused K+ efflux only at a much higher concentration (2mM). It was shown that induction of K+ efflux by DCCD was not mediated via inhibition of ATPase and that it may be the result of a direct effect of the drug on the cell membrane or on the K+ carrier. All three inhibitors also caused mild hyperpolarization of the membrane and an increase in the carrier mediated Ca2+ uptake into the cells. The increase in delta psi balanced the decrease in delta pH so that the value of delta mu H+ changed very little following incubation of the cells with the inhibitors. The respiratory deficient mutant ('petite') displayed similar phenomena to the wild type, but membrane potential values were lower than in the wild type.

Physiological and enzymatic properties of a thymidine-requiring Pediococcus cerevisiae mutant.

We describe the isolation and characterization of a Pediococcus cerevisiae thymidine-requiring mutant and its thymidine-independent revertant. The mutant strain lacked thymidylate synthetase activity and had an absolute requirement for low concentrations (2 micrograms/ml) of thymidine in addition to a requirement for N-5-formyl tetrahydrofolic acid (folinate). Even at high concentrations (up to 500 micrograms/ml), thymine could not replace thymidine. In contrast to its wild-type parent, which grows only on folinate, the thymidine-requiring mutant (Thy- Fol+) was able to take up and grow on picogram quantities of unreduced folic acid. When both strains were grown on folinate, the Thy- Fol+ strain was at least 10(3)-fold more resistant to the folic acid analogs aminopterin and methotrexate than the wild-type strain. On the other hand, when grown on folic acid, the Thy- Fol+ strain was as sensitive to the folic acid analogs as the Thy+ Fol+ strain and was 10(2)-fold more sensitive than the wild-type strain grown on folinate. The thymidine-independent revertant (Thy+ Fol+) regained the wild-type level of thymidylate synthetase activity, but maintained the ability to take up and grow on unreduced folic acid like its Thy- Fol+ parent.