Glycine transport by hemolysed and restored pigeon red cells. Effects of a Donnan-induced electrical potential on entry and exit kinetics.

The influence of a Donnan effect on the transport of glycine by hemolysed and restored pigeon red cells was examined. The Donnan effect was produced by replacing Cl- with 2,4-toluenedisulfonate or glutamate. The effects of the associated membrane potential and inside-outside pH difference on glycine entry and exit rates were examined. The effects of pH on entry and exit rates in the absence of a Donnan effect were also examined. In the absence of a Donnan effect, Na+-dependent glycine entry requires the protonated form of a group with a pKapp of 7.9 and the deprotonated form of another group with a pKapp of 6.8. Neither of these are required for exit but the deprotonated form of a group(s) with a pKapp of 6.2 is required. The pK 7.9 group and pK 6.2 group probably react with H+ at the inner face of the membrane and the pK 6.8 group probably reacts at the outer face. The V for glycine entry was determined for cells with their Cl- largely replaced by toluenedisulfonate and without such replacement. Between pH 6.1 and 7, the ratio of the respective V values, VT/VC1, was 1.5-1.7. VT/VC1 rose above pH 7 to near 4 at pH 8.3. At pH 6.9, with glutamate replacing cell Cl-, the analogous ratio (VGlu/VC1) was 1.7. The increase of VT/VC1 above pH 7 could be quantitatively accounted for by the increase in cell [H+]/medium [H+] caused by the Donnan effect together with the assumption that the pK 7.9 group reacts with H+ at the inner face of the membrane. When cell Cl- was replaced by toluenedisulfonate or glutamate there was a drop in the term in the glycine Km describing Na+ dependence of glycine entry. When cell Cl- was replaced by toluenedisulfonate therewas a rise in the Na+-independent term in the glycine entry Km. By replacing varying amounts of cell Cl- with either toluenedisulfonate or glutamate, plots were obtained of entry rates vs. the cell [Cl-]/ medium [Cl-] ratio consistent with the assumption that the Donnan-induced membrane potential acts on a "moving" charge. Glycine exit was only slightly accelerated by trans-toluenedisulfonate. The ratio, exit rate into toluenedisulfonate medium/exit rate into Cl- medium rose with decreasing pH. This rise could be accounted for by a Donnan-induced inside-outside pH difference which affects a pKapp 6.2 group reacting with internal H+. The observed influences of the Donnan effect on V (glycine entry), on both components of Km (glycine entry), on the shape of the plot of glycine entry rate vs. the cell [Cl-]/medium [Cl-] ratio and on glycine exit all fit the assumptions that when the empty porter reorients, one unit of negative charge accompanies it "across" the membrane and that no other steps involve charge movement. The properties of the system seem inconsistent with a translational ("ferry boat") mobile carrier.

Differential effects of 5-HT1B/1D receptor agonists on neurogenic dural plasma extravasation and vasodilation in anaesthetized rats.

These studies compared the effects of the 5-HT1B/1D receptor agonists sumatriptan, CP-122 288 ((R)-N-methyl-[3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl] methanesulphonamide succinate) and CP-93 129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one dihydrochloride) on neurogenic dural extra-vasation and vasodilation in anaesthetized rats. Dural extravasation, evoked by high intensity (1.2 mA) stimulation of the trigeminal ganglion, was measured using the radioactive plasma marker 125I-labelled bovine serum albumin. Dural vasodilation produced by lower intensity (50-300 microA) stimulation of trigeminal fibres, was measured through a closed cranial window using intravital microscopy. All compounds inhibited dural extravasation (rank order of potency: CP-122 288 > > sumatriptan > CP-93 129) and dural vasodilation (rank order of potency: CP-93 129 > > sumatriptan = CP-122 288). Comparison of the potency of these compounds with their potencies in an in vitro functional model, agonist-induced [35S]GTP gamma S binding, suggests that blockade of dural extravasation was consistent with an action at rat 5-HT1D receptors, but activity at another, unknown, "extravasation receptor" could also be involved. In contrast, inhibition of dural vasodilation was consistent with an action at rat 5-HT1B receptors. We suggest that in our preparations, production of dural vasodilation involves activation of trigeminal A delta-fibres whereas production of dural extravasation involves activation of trigeminal C-fibres. The differential effects of compounds on dural extravasation and vasodilation may therefore be due to the different receptor subtypes involved and to the selective localization of these subtypes on different populations of trigeminal sensory fibre.

Functional status as an overall measure of health in adults with cystic fibrosis: further validation of a generic health measure.

We studied the validity of a generic health measure in a population with a chronic, life-shortening illness. Thirty-seven adults with cystic fibrosis (CF) and 46 of their healthy peers completed a questionnaire which included 12 questions on functional status from the RAND Health Insurance Study. For the CF group, the questionnaire and a medical chart review yielded data on 7 additional health variables, including pulmonary function. After data collection, members of the CF group were followed for 5 years, by which time 11 had died. The functional status of the CF group was significantly lower than that of the comparison group. Within the CF group, functional status correlated significantly with 6 of the 7 other health variables. Analysis using the Cox proportional hazards model showed that functional status alone was a significant (p less than 0.001) predictor of a CF subject's survival time; in a multivariate model a non-significant trend suggested that lowered functional status may be associated with an increased risk of early death even after adjustment for pulmonary function and percent ideal body weight. These results extend previous findings and suggest that functional status can be used as an overall measure of health in a wide variety of studies.

A comparative study of the psychosocial assets of adults with cystic fibrosis and their healthy peers.

Psychosocial assets of 37 adults with cystic fibrosis (CF) and 46 of their healthy peers were assessed by mailed questionnaire. Major sociodemographic variables did not differ significantly between the two groups, nor did indices of emotional social support, social network density, self-esteem, or current life satisfaction. This study revealed adults with CF to function on a par with their healthy peers in nearly all respects, a finding at odds with those from uncontrolled studies and which suggests to us that many previous conclusions about the psychosocial health of adults with CF have been unwarranted. Future psychosocial studies involving patients with CF should include control groups and inferences about the effect of these patients' physical illness on their psychosocial health should not be made in the absence of normative data.

The increased incidence on Mondays of work-related sprains and strains.

Insurance-industry researchers have shown an increase on Mondays of lost-time sprain and strains said to be work-related, but thought to be fraudulent claims for off-the-job weekend injuries. We examined this issue among civilian employees of the Department of the Navy, using data from claims for injuries occurring between 1989 and 1994. We found that the rate of Monday sprains and strains significantly exceeded the expected rate and that such claims were significantly more likely to be made by claimants who were craftsmen and mechanics, who reported an injury to the back or trunk, who were supervisors, or who did not have college degrees. We estimate that 22% of claims for Monday-occurring sprains and strains are possibly fraudulent and that their cost to the Department of the Navy during the 6 years studied was $38 million. For the entire federal government, cost for such claims during this period may have exceeded $250 million.

Quadrupole moments of highly deformed structures in the A approximately 135 region: probing the single-particle motion in a rotating potential.

The latest generation gamma-ray detection system, GAMMASPHERE, coupled with the Microball charged-particle detector, has made possible a new class of nuclear lifetime measurement. For the first time differential lifetime measurements free from common systematic errors for over 15 different nuclei ( >30 rotational bands in various isotopes of Ce, Pr, Nd, Pm, and Sm) have been extracted at high spin within a single experiment. This comprehensive study establishes the effective single-particle transition quadrupole moments in the A approximately 135 light rare-earth region. Detailed comparisons are made with theoretical calculations using the self-consistent cranked mean-field theory which convincingly demonstrates the validity of the additivity of single-particle quadrupole moments in this mass region.