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R S Lewis

Publications and source records attributed to R S Lewis.

At least 73 records · Page 4Linked to original sources
PubMed1989

Mitogen-induced oscillations of cytosolic Ca2+ and transmembrane Ca2+ current in human leukemic T cells.

A rapid rise in the level of cytosolic free calcium ([Ca2+]i) is believed to be one of several early triggering signals in the activation of T lymphocytes by antigen. Although Ca2+ release from intracellular stores and its contribution to Ca2+ signaling in many cell types is well documented, relatively little is known regarding the role and mechanism of Ca2+ entry across the plasma membrane. We have investigated mitogen-triggered Ca2+ signaling in individual cells of the human T-leukemia-derived line, Jurkat, using fura-2 imaging and patch-clamp recording techniques. Phytohemagglutinin (PHA), a mitogenic lectin, induces repetitive [Ca2+]i oscillations in these cells peaking at micromolar levels with a period of 90-120 s. The oscillations depend critically upon Ca2+ influx across the plasma membrane, as they are rapidly terminated by removal of extracellular Ca2+, addition of Ca(2+)-channel blockers such as Ni2+ or Cd2+, or membrane depolarization. Whole-cell and perforated-patch recording methods were combined with fura-2 measurements to identify the mitogen-activated Ca2+ conductance involved in this response. A small, highly selective Ca2+ conductance becomes activated spontaneously in whole-cell recordings and in response to PHA in perforated-patch experiments. This conductance has properties consistent with a role in T-cell activation, including activation by PHA, lack of voltage-dependent gating, inhibition by Ni2+ or Cd2+, and regulation by intracellular Ca2+. Moreover, a tight temporal correlation between oscillations of Ca2+ conductance and [Ca2+]i suggests a role for the membrane Ca2+ conductance in generating [Ca2+]i oscillations in activated T cells.

Calcium↗
PubMed1988

Subset-specific expression of potassium channels in developing murine T lymphocytes.

Ion channels were studied in four major subsets of developing murine thymocytes by using patch-clamp recording and cell-surface staining techniques. The expression of three types of voltage-gated potassium channels in thymocytes varies consistently with the cell's developmental state and functional class as defined by cell-surface markers. One class of potassium channel (type n) predominates in immature thymocyte subsets as well as in mature-phenotype CD4+CD8- thymocytes (precursors to helper T lymphocytes), and the average surface density of this channel type correlates with the extent of cell proliferation. Two additional types of potassium channels (types n' and l) are found in the mature CD4-CD8+ thymocyte subset that contains precursors to cytotoxic and suppressor T cells. The subset-specific expression of type n' and l potassium channels suggests their use as additional cell-surface markers with which to identify precursors to the cytotoxic suppressor T cell lineage.

Animals↗
PubMed1988

The relationship between cerebral lateralization and cognitive ability: suggested criteria for empirical tests.

Many recent investigations in cognitive neuropsychology have been devoted to a fundamental question: are individual differences in cerebral lateralization reliably associated with differences in cognitive ability? The results have been highly inconsistent and inconclusive, with some studies showing a relationship, others not. We propose that research on this question has been hampered by inadequate clarification of the criteria required for a proper test. We suggest what these criteria should be, and, for purposes of illustration, we evaluate representative tests of the lateralization--cognition hypothesis in light of these criteria. We conclude that studies that meet our criteria lend at least a modest measure of support for the hypothesis.

Cognition↗
PubMed1988

Kinetic analysis of voltage- and ion-dependent conductances in saccular hair cells of the bull-frog, Rana catesbeiana.

1. By the use of whole-cell and excised-patch tight-seal recording techniques, we studied ionic conductances in voltage-clamped solitary hair cells isolated from the bull-frog's sacculus. As a basis for assessing their contributions to hair cell electrical resonance, we developed kinetic models describing voltage-dependent Ca2+ and Ca2+-dependent K+ conductances. 2. A transient K+ current (IA) was activated by steps to potentials positive to -50 mV from holding potentials more negative than -70 mV. In the steady state, the current was fully inactivated at the normal resting potential. Possibly due to the dissipation of a Donnan potential between the pipette's interior and the cell, the voltage dependence of IA inactivation slowly shifted in the negative direction during whole-cell recording. 3. The voltage-gated Ca2+ current (ICa) was isolated by blocking IA with 4-aminopyridine (4-AP) and Ca2+-activated K+ current with tetraethylammonium (TEA). The ICa was activated at potentials more positive than -60 to -50 mV and was maximal at about -10 mV. Its magnitude was highly variable among cells, with an average value of -240 pA at -30 mV. Its activation could be fitted well by a third-order (m3) gating scheme. 4. A Ca2+-activated K+ current (IK(Ca)) was isolated as the component of membrane current blocked by TEA. This current was activated at potentials more positive than -60 to -50 mV and had an average value of 1.5 nA at -30 mV. The Ca2+-activated K+ conductance (gK(Ca)) showed a high apparent voltage dependence, increasing e-fold every 3 mV at potentials between -50 and -40 mV. 5. The Ca2+-activated K+ current displayed rapid activation and deactivation kinetics. The current reached half-maximal activation in 2-4 ms at voltages between -50 and -30 mV, and the tail current decayed exponentially with a time constant of 1.0 ms at -70 mV. The activation rate and magnitude of IK(Ca) were reduced by lowering the extracellular Ca2+ concentration. 6. The open probability of Ca2+-activated K+ channels was estimated by ensemble-fluctuation analysis of whole-cell currents evoked by voltage steps to -30 mV. The average open probability was estimated to be 0.8 at this potential. 7. K+-selective channels with a high conductance (140-200 pS) were examined in excised, inside-out membrane patches. The activity of these channels depended on intracellular Ca2+ and membrane potential. These properties suggest that the channels underlie the whole-cell Ca2+-activated K+ current.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1988

A model for electrical resonance and frequency tuning in saccular hair cells of the bull-frog, Rana catesbeiana.

1. Electrical resonance in solitary hair cells was examined under several experimental conditions using the tight-seal recording technique in the whole-cell current-clamp mode. 2. Resonance was characterized by the frequency and quality factor of oscillations in membrane potential evoked by depolarizing current pulses. Oscillation frequency increased with depolarization, from about 90 Hz at the resting potential to a limiting value of about 250 Hz. The quality factor of the oscillations was a bell-shaped function of membrane potential that reached a maximum of up to 12.6 at a potential slightly positive to the resting potential. 3. Pharmacological experiments were performed to assess which of three ionic currents participate in electrical resonance. Reduction of the voltage-gated Ca2+ current (ICa) and the Ca2+-activated K+ current (IK(Ca)) by lowering the extracellular Ca2+ concentration, or reduction of IK(Ca) with tetraethylammonium ion (TEA) degraded the resonance. In contrast, blockade of the transient K+ current (IA) with 4-aminopyridine (4-AP) had no significant effect. 4. To test the sufficiency of the Ca2+ and the Ca2+-activated K+ currents to account for resonance, we developed a model using mathematical descriptions of the two currents derived in the preceding paper (Hudspeth & Lewis, 1988), with additional terms for leakage conductance and membrane capacitance. The model correctly predicts the oscillatory responses to applied current pulses, including the non-linear dependences of oscillation frequency and quality factor on membrane potential. 5. Simulations of current-clamp experiments in the presence of a reduced extracellular Ca2+ concentration or of TEA were generated respectively by decreasing the model's values for the maximal Ca2+ or Ca2+-activated K+ conductances. The model's predictions of membrane-potential oscillations under these conditions agree qualitatively with experimental results, providing further support for the model as a description of the resonance mechanism. 6. To identify the factors most important in determining the hair cell's resonance properties, we systematically altered the values of selected parameters in the model. Frequency was most profoundly influenced by increasing the magnitude and activation rate of the Ca2+-activated K+ conductance, whereas the quality factor was most sensitive to increases in the level of the Ca2+ conductance. 7. By including a term describing activation of the hair cell's mechanically sensitive transduction conductance, we used the model to predict a tuning curve for responses to mechanical inputs of various frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1988

Individual differences in the cerebral organization of language using input and output interference measures of lateralization.

The literature on the relationship between cerebral lateralisation and the combined effects of sex and handedness, reveals many discrepant findings. In an effort to clarify these discrepancies, three different types of interference cerebral lateralization tasks were used in a relatively large sample of normal individuals. Handedness differences were found in the expected direction on all three lateralization measures: input interference (dichotic listening), and two output interference measures, a motor-motor interference task (concurrent finger tapping and verbal fluency) and a motor-cognitive interference task (concurrent finger tapping and silent reading). A sex difference, however, was found on only the motor-motor interference task. These results suggest that possible sex differences in cerebral lateralisation may be less prominent among particular types of interference laterality tasks, and more reliably found with motor-motor interference lateralization measures.

Journal Article↗
PubMed1987

Sex differences in spatial task performance of patients with and without unilateral cerebral lesions.

Two visuospatial tasks, the WAIS Block Design and the Street Gestalt Completion Test, were administered to men and women with and without unilateral cerebral lesions. These two tasks represent different categories of visuospatial functions. The Street test is a visual-perceptual gestalt task, requiring the closure of fragmented pictures, whereas Block Design is an analytical, manipulospatial task requiring rotation of spatial coordinates. For the non-brain-damaged group, the men showed a nonsignificant trend toward better Block Design performance relative to the women, whereas there was no sex-related difference in Street performance. For the brain-damaged groups, patients with right hemisphere lesions performed significantly worse than patients with left hemisphere lesions on both the Street test and Block Design, indicating that both tasks were more sensitive to right hemisphere functioning. There was, however, a significant sex X side of lesion interaction on Block Design only, with the men showing a more asymmetrical pattern of scores. These results suggest that sex differences in functional lateralization may underlie sex differences in visuospatial ability, and that sex differences in functional lateralization may be present for only certain visuospatial processes.

Adult↗
PubMed1980

A model for the activation and inactivation of neocarzinostatin, an antitumor protein.

Sulfhydryl compounds specifically activate and inactive neocarzinostatin as measured by the in vitro strand scission of T2 DNA. This effect, and evidence for strained disulfides in the molecule, leads us to propose a model of activation and inactivation. We suggest that neocarzinostatin reacts with sulfhydryl reagents to produce a short-lived active form which may react with DNA or proceed irreversibly via a conformational change to an inactive form (preneocarzinostatin). Three parameters of neocarzinostatin activity (inactivation rate, single strand break plateau position, and initial single strand break rate), have been measured for various sulfhydryl concentrations, and the observed results agree well with values expected from a simplified mathematical treatment of the model, thus supporting the assumptions made.

Antibiotics, Antineoplastic↗
PubMed1980

The generalization of pre-neocarzinostatin and antagonism of neocarzinostatin-induced DNA scission in vitro.

Pretreatment of the antitumor protein neocarzinostatin with heat, ultraviolet or white light, and thiols inactivates the drug, as measured by the cessation of phage T2 DNA strand scission in vitro. The inactive forms obtained are identical with pre-neocarzinostatin on the basis of isoelectric focusing, molecular weight determination, and changes in circular dichroism spectra. In incubations together with neocarzinostatin and T2 DNA, the inactive form inhibits strand scission to a considerable degree. This result suggests that both forms compete for a limited number of available DNA binding sites.

Antibiotics, Antineoplastic↗
PubMed1975

Condensation time of the solar nebula from extinct I in primitive meteorites.

Mineral separates from five carbonaceous chondrites were dated by extinct 16 million year (129)I, in an attempt to establish the condensation time of the solar nebula. Two Fe(3)O(4) or Fe(3)O(4)-FeS samples from the Murchison and Orgueil meteorites are older than any other material dated thus far, and apparently formed within 2 x 10(5) years of each other. The great age, close isochronism, and primitive nature of the samples suggest that the event recorded was the condensation stage of the solar nebula. It provides a suitable zero point for the chronology of the early solar system. The (129)I/(127)I ratio during condensation of the nebula was (1.46 +/- 0.04) x 10(-4). The recrystallized C4 chondrite Karoonda began to retain (129)Xe 1.8 +/- 0.5 million years after the above event. This short cooling time implies rapid aceretion (</=1 million years) and a shallow origin (</=10 km) below the surface of its parent body.

Journal Article↗
PubMedDate not supplied

Effects of morphine on acquisition and maintenance of ethanol and water intake patterns in rats.

Two experiments were conducted to assess the effects of chronic subcutaneous injections of morphine (1.0 mg/kg) or saline on the pattern and amount of sweetened ethanol and water intake in fluid restricted Long-Evans rats. Following daily injections, 2-h two-bottle choice tests were conducted with water and an ethanol solution (15% ethanol v/v in 5% sucrose w/v). During a 20-day acquisition phase (Experiment 1), ethanol intake patterns and amounts did not differ between saline (n = 6) and morphine (n = 6) groups. Both groups exhibited ethanol intake patterns that decreased exponentially throughout the session suggesting control by fluid restriction procedures. Morphine decreased water intake during initial periods of each session and increased intake during later periods. In Experiment 2, morphine and saline injections were reversed across three phases with the same rats. Morphine increased total ethanol consumption during the first few days of each 15-day phase, but the groups did not differ thereafter, and the initial increases produced no statistically significant group differences. Additionally, morphine augmented ethanol intake in early portions of sessions, while water intake was decreased and increased during early and later portions of each session, respectively. Analysis of the data from the last 5 days of each phase indicated that, when injected with morphine, the group which received saline during acquisition consumed significantly more ethanol solution than the group injected with morphine during acquisition. The effect on patterns of water and ethanol intake were observed, regardless of the drug injected during acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗