Showing papers by "David W. Johnson published in 1989"

Cooperation and Competition: Theory and Research

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New antitumor monoclonal antibody-vinca conjugates LY203725 and related compounds: design, preparation, and representative in vivo activity.

Abstract: A method has been developed to allow the direct coupling of the cytotoxic vinca alkaloid 4-desacetylvinblastine-3-carbohydrazide (DAVLB hydrazide) to a variety of murine monoclonal antibodies directed against human solid tumors. Periodate oxidation of carbohydrate residues on the antibodies, followed by reaction with DAVLB hydrazide in aqueous acid affords, in most cases, conjugates with conjugation ratios of 4-6 vincas per antibody in high yield without significantly impairing antigen binding or solubility. The outcome of the conjugation reaction is highly dependent on the concentration of, and time of exposure of the protein to, the oxidant. These conjugates exhibit potent antitumor activity in vivo against a number of human solid tumor-nude mouse xenografts, with efficacy and safety increased over unconjugated DAVLB hydrazide. This antitumor activity is also superior to that of similarly prepared but nontarget tumor binding antibody-DAVLB hydrazide conjugates. MoAb-DAVLB hydrazide conjugates release DAVLB hydrazide in solution in a temperature- and pH-dependent manner. Hydrolytic release of unmodified DAVLB hydrazide from tumor-localized MoAb-DAVLB hydrazide conjugates in vivo may be an important factor in their antitumor activity.

Impact of Goal and Resource Interdependence on Problem-Solving Success

Abstract: Despite the considerable evidence that cooperation promotes higher individual achievement and greater group productivity than do competitive or individualistic situations, there are conditions under which the opposite may be true. The relative impact of positive goal interdependence and positive resource interdependence on individual achievement and group productivity in a computer-assisted problem-solving task was investigated. Forty-four Black American high school seniors and college freshmen, stratified for ability, sex, and urban or rural background, were randomly assigned to conditions. Positive goal interdependence promoted higher individual achievement and group productivity than did no goal interdependence. The combination of positive goal and resource interdependence promoted higher individual achievement and group productivity than did any of the other conditions, indicating that two sources of positive interdependence are more powerful than one. When used in isolation from positive goa...

Collaborative Skill Instruction for Promoting Positive Interactions between Mentally Handicapped and Nonhandicapped Children

Abstract: Structuring cooperative learning activities has been shown to be an effective technique for integrating handicapped and nonhandicapped students. Previous research in this area has focused on the relative effects of cooperative versus competitive and individualistic learning situations upon peer relations and academic achievement. Few investigations have examined the various elements within the cooperative learning model that appear to promote positive peer interactions among handicapped and nonhandicapped students. The present study evaluated the influence of collaborative skill instruction versus no collaborative skill instruction on the social interaction behaviors of moderately/severely handicapped and nonhandicapped students participating in group science activities. These data reveal that students receiving collaborative skill instruction interacted more positively with one another than those who did not receive the instruction.

Kinetic facial selectivity in nucleophilic displacements at tetracoordinate phosphorus: kinetics and stereochemistry in the reaction of sodium ethoxide with O,S-dimethyl phenylphosphonothioate

Abstract: Les auteurs demontrent que le deplacement de l'ion methylthiolate du thiophosphonate du titre, par l'ion ethanolate s'effectue avec une inversion complete de configuration du phosphore

Synthesis and biological evaluation of omega-(N,N,N-trialkylammonium)alkyl esters and thioesters of carboxylic acid nonsteroidal antiinflammatory agents.

Abstract: A series of novel ω-(N,N,N-trialkylammonium)alkyl ester and thioester derivatives [RCOM(CH2) n NR3+X−, M = O or S, n = 2–6, X = I or Cl] of 11 nonsteroidal antiinflammatory carboxylic acid agents (naproxen, ketorolac, indomethacin, ibuprofen, sulindac, ketoprofen, flufenamic acid, mefenamic acid, zomepirac, etodolac, and tifurac) was prepared and evaluated for their antiinflammatory, analgesic, and gastrointestinal erosive properties In general, each prodrug retained the antiinflammatory activity characteristic of the corresponding parent drug but exhibited moderately to greatly reduced gastrointestinal erosive properties and significantly reduced analgetic potencies This profile is likely due to a combination of factors including the rate of hydrolysis of the esters in the stomach, gut, and plasma, changes in the locus of absorption of the prodrug or nonsteroidal antiinflammatory drug (NSAID), and altered metabolic disposition patterns resulting from these changes The results obtained from the compounds of this series indicate that esters of this general class may offer a means to modulate both the aqueous/lipid solubility and the hydrolytic/enzymatic cleavage indices of NSAID prodrugs which potentially possess a more favorable therapeutic ratio of antiinflammatory to gastrointestinal erosive activities

CSF acidosis augments ventilation through cholinergic mechanisms.

Abstract: Ventilation is influenced by the acid-base status of the brain extracellular fluids (ECF). CO2 may affect ventilation independent of changes in H+. Whether the acidic condition directly alters neuronal firing or indirectly alters neuronal firing through changes in endogenous neurotransmitters remains unclear. In this work, ventriculocisternal perfusion (VCP) was used in anesthetized (pentobarbital sodium, 30 mg/kg) spontaneously breathing dogs to study the ventilatory effects of acetylcholine (ACh), eucapnic acidic (pH approximately 7.0) cerebrospinal fluid (CSF), and hypercapnic acidic (pH approximately 7.1) CSF in the absence and presence of atropine (ATR). Each animal served as its own control. Base line was defined during VCP with control mock CSF (pH approximately 7.4). With ATR (4.8 mM) there was an insignificant downward trend in minute ventilation (VE). ACh (6.6 mM) increased VE 53% (n = 12, P less than 0.01), eucapnic acidic CSF increased VE 41% (n = 12, P less than 0.01), and hypercapnic acidic CSF increased VE 47% (n = 6, P less than 0.01). These positive effects on ventilation were not seen in the presence of ATR. This suggests that acidic brain ECF activates ventilatory neurons through muscarinic cholinergic mechanisms. Higher concentrations of ACh increased ventilation in a concentration-dependent manner. Higher concentrations of ATR decreased ventilation progressively, resulting in apnea. The results suggest that ACh plays a significant role in the central augmentation of ventilation when the brain ECF is made acidic by either increasing CSF PCO2 or decreasing CSF bicarbonate.

Impurity transport in ohmically heated TFTR plasmas

Abstract: The paper presents a study of impurity transport in ohmically heated TFTR plasmas by computer modelling of VUV line emissions from impurities injected using the laser blow-off technique. The results are sensitive to uncertainties in the ionization and recombination rates used in the modelling and, therefore, only a spatially averaged diffusion coefficient and parameterized convective velocity can be measured. Measurements of these transport parameters are presented for deuterium and helium discharges with Ip = 0.8−2.5 MA, e = (0.6-6.0) × 1019 m−3 and Zeff = 2-6. The diffusion coefficients are found to be in the range of 0.5-1.5 m2 s−1, considerably larger than neoclassical values. Non-zero inward convective velocities are necessary to fit the data in most cases. No dependence of the diffusion coefficient on injected element, working gas species or plasma current is found, but, at a given current, the diffusion coefficient in plasmas near the density limit is smaller by approximately a factor of two than in discharges with e < 3 × 1019 m−3.

Metabolism of saturated and polyunsaturated fatty acids by normal and Zellweger syndrome skin fibroblasts.

Abstract: The metabolism of 1-11C-labelled derivatives of palmitic (C16:0), arachidonic (C20:4,n-6) lignoceric (C21:0) and tetracosatetraenoic (C24:4,n-6) acids was studied in normal skin fibroblast cultures and in cultures of fibroblasts from peroxisome-deficient (Zellweger's syndrome) patients. Radiolabelled products of the fatty acids included carbon dioxide. C14-24 saturated and mono-unsaturated fatty acids formed from released acetate either by synthesis de novo or by elongation of endogenous fatty acids, fatty acids formed by 2-6-carbon elongation of added substrates, and a number of water-soluble compounds, some of which were tentatively identified as the amino acids glutamine, glutamic acid and asparagine. The labelled amino acids were found predominantly in the culture medium. Zellweger's syndrome fibroblasts showed a marked decrease in radiolabelled carbon dioxide and water-soluble-product formation from (I-14C)-labelled arachidonic, tetracosatetraenoic and lignoceric acids but not from [I-14C]palmitic acid, and the production of radiolabelled C14-18 fatty acids was also diminished. However, the elongation of individual fatty acids was either normal or above normal. Our data support the view that the oxidation of 20:4, 24:4 and 24:0 fatty acids in cultured skin fibroblasts takes place largely in peroxisomes, and further that the acetyl-CoA released by the beta-oxidation process is available for the synthesis of fatty acids and amino acids. We speculate that the generation of C2 units used for synthesis is a major peroxisomal function and that this function is absent or greatly impaired in Zellweger's syndrome cells.

Effects of hypercapnia on brain pHi and phosphate metabolite regulation by 31P-NMR.

Abstract: The ability of brain cells to regulate intracellular pH (pHi) and several phosphate metabolites was evaluated during 1 h of hypercapnia (inspiratory CO2 fraction of 0.10 and 0.05) in anesthetized rats by 31P high-field (145.6 MHz) nuclear magnetic resonance spectroscopy. Body temperature was maintained at 37 +/- 0.5 degrees C. Fully relaxed spectra were obtained for controls and 30–50 min after CO2 loading and CO2 withdrawal. Spectra were taken serially every 2.5 min after gas mixtures were changed. Brain pHi decreased 0.10 +/- 0.02 units [7.06 +/- 0.01 (SE)] to 6.96 +/- 0.01 (P less than 0.001) after 30–50 min of 10% CO2 breathing, and arterial pH decreased 0.24 +/- 0.01 units. Brain pHi decreased by 0.045 +/- 0.01 units (7.05 +/- 0.01 to 7.01 +/- 0.01, P less than 0.05) during 5% CO2 breathing. Brain pHi returned to control values after 30–50 min of CO2 washout in both groups. In three of six animals breathing 10% CO2, there was an undershoot in brain pHi by 0.07–0.09 units between 2.5 and 20 min of hypercapnia. Three animals exhibited an overshoot in pHi by 0.06–0.11 units between 7.5 and 17.5 min during CO2 washout. Phosphocreatine-to-Pi and Pi-to-beta-ATP ratios changed during hypercapnia and returned to base line after withdrawal of CO2. The findings of a smaller brain pHi change than arterial pH change and undershoots and overshoots in pHi support the view that pHi regulation involves active processes such as transmembrane ion transport.

Effects of hypothermia on rat brain pHi and phosphate metabolite regulation by 31P-NMR.

Abstract: The effects of arterial alphastat regulation on brain intracellular pH (pHi) and several phosphate metabolites were assessed in anesthetized rats during hypothermia (28.6 +/- 0.2 degrees C) and normothermia (36.2 +/- 0.2 degrees C) by using 31P high-field (8.5 T) nuclear magnetic resonance (NMR). There were significant differences in pHi and metabolite ratios at the two temperatures under conditions of equal minute ventilation. During hypothermia, the brain pHi was 0.09 U higher, the phosphocreatine-to-inorganic phosphate (PCR/Pi) ratio 49% larger, and Pi-to-ATP 20% lower than at normothermia. These changes were fully reversible on warming the animal. The change in brain pHi/temperature was -0.011U/degrees C (95% confidence interval -0.007 to -0.016). The brain's ability to regulate its pHi and phosphate metabolism during hypercapnic acid-base stress was studied by using 10% CO2 ventilation. Hypothermic rats showed a larger fall in brain pHi (0.145 +/- 0.01 U, 7.15-7.01) with 10% CO2 than normothermic rats (0.10 +/- 0.02 U, 7.06-6.96). Similarly ventilated rats had a larger fall in arterial pH with 10% CO2 at hypothermia (0.36 +/- 0.04 U) than normothermia (0.24 +/- 0.01 U), so the delta brain pH/delta arterial pH was the same at both temperatures. The brain PCr-to-Pi ratio decreased approximately 20% during 10% CO2 breathing in both hypothermic and normothermic animals. Brain pHi and metabolite ratios returned to base line 30-50 min after CO2 washout in both groups. In summary, lowering body temperature while maintaining constant ventilation leads to changes in brain pHi and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Electron temperature profile behaviour in TFTR during neutral beam injection and multiple pellet fuelling

Abstract: The electron temperature profiles on the Tokamak Fusion Test Reactor (TFTR) are determined by several diagnostics, including multi-point Thomson scattering and electron cyclotron emission measured with heterodyne radiometers and a Michelson interferometer The electron temperature profiles are characterized by very high central temperatures (>8 keV) and large Shafranov shifts (>35 cm) The large Shafranov shifts suggest the necessity of mapping to magnetic flux surfaces when investigating the profile behaviour During 1986 ,TFTR was operated with up to 20 MW of deuterium neutral beam injection (NBI) and a deuterium pellet injector The electron temperature profile measurements were made on plasmas with 27 < BT < 51 T, βpdia up to 22, 1 × 1019

Plasma polyenoic very-long-chain fatty acids in peroxisomal disease: biochemical discrimination of Zellweger's syndrome from other phenotypes.

Abstract: The plasma of patients with inherited defects in peroxisomal biogenesis (ie, Zellweger9s syndrome, infantile Refsum9s disease, and neonatal adrenoleukodystrophy) shows evidence of a disturbance in the metabolism of saturated and monoenoic fatty acids with carbon chain lengths greater than 22 (VLCFA). Zellweger9s syndrome plasma alone contains, in addition, increased amounts of a number of n-6 polyenoic VLCFA including 24:5, 26:5, 28:5, 30:5, and 30:6 fatty acids. These fatty acids facilitate the biochemical discrimination of Zellweger9s syndrome from other related phenotypes.

Studies of Myelin Breakdown in Vitro

Abstract: The present chapter describes that aspect of our studies that is concerned with the mechanism of myelin sheath damage in inflammatory demyelinating diseases such as multiple sclerosis (MS) and Guillain-Barre syndrome (GBS). Our work has been largely conducted in vitro, and most of it has been concerned with biochemical changes occurring in myelin under a variety of pathologically relevant challenges. Although not intended as a detailed review of the biochemistry of demyelination, the results we have obtained will be discussed with respect to related studies, the problems in interpreting these findings, and ways in which our results may relate to the pathogenesis of human disease. Inflammatory diseases can affect both central nervous system (CNS) and peripheral nervous system (PNS) myelin, and although most of the experiments described here involve the CNS, thee mechanism of PNS sheath breakdown may well have features in common.

Impact of Cooperative-Team Learning on Performance and Retention of Navy Air-Traffic Controller Trainees

Abstract: : Cooperative-team learning was compared with traditional Navy instruction and success was measured by the ability to master technical information and to perform a conceptually complex task. With several classes of air traffic control trainees and ROTC students, it was demonstrated that cooperative-team learning led to: (a) greater learning; (b) greater ability to perform job functions; (c) a zero rate of failure compared to an average of 2 under traditional instruction; (d) greater esprit de corps; (e) more positive perception of instructor competence; and (f) greater effort to learn and the perception that the materials were less difficult. Cooperation was structured by goal interdependence, i.e., the perception that one achieve one's goal if and only if all other group members achieve their goals, and by resource interdependence, i.e., the perception that resources are divided so that each group member has only a portion of the resources needed for the task to be completed. Goal interdependence produced higher achievement, more effective interaction, and greater perception of student and instructor support.

Impact of Cooperative-Team Learning on Performance and Retention

Abstract: : Three studies were conducted. Two investigated the impact of cooperative team learning, compared with traditional Navy instruction, on the independent functional ability to master technical information and use it to perform a conceptually complex job, the failure rate within Navy training programs, and the social integration of heterogeneous trainees into cohesive work groups characterized by esprit-de-corps. One investigated the impact of goal and resource interdependence on performance and attitudes of ROTC students. The first study involved teaching a class of 13 air traffic control trainees the Charts and Publications Unite. The second study utilized two classes of air traffic control trainees studying the Charts and Publications Unit. The results from the two studies indicate that cooperative-team learning, compared with traditional instruction, results in: 1. Greater learning of technical information. 2. Greater independent functional ability to perform job functions. 3. A zero failure rate (compared with and average of 2.14), even with trainees who had failed previous units and were judged to be incapable of the academic requirements of the training program. Greater effort to learn and a perception of the material to be learned as being less difficult. The third study compared two ways of structuring cooperation: goal interdependence (the perception that one can achieve one's goal is and only if all other group members achieve their goals) and resource interdependence (the perception that resources are divided so that each group member has only a portion of the resources need for the task to be completed).

Isotope labelling of lipids using the Favorsky rearrangement

Abstract: The synthesis of tetradeuterated 10-methylundecanoic acid, dideuterated tetracos-2-enoic acid, (1-14C)pristanic acid and (1-14C)tetracos-2-enoic acid using the Favorsky rearrangement are described. They will be used for studies of long-chain fatty acid metabolism in patients. The positions of isotope labelling were determined by mass spectrometry.

Energy confinement time and electron density profile shape in TFTR [Tokamak Fusion Test Reactor]

Abstract: The electron density profiles of intense deuterium neutral-beam- heated plasmas (P{sub tot}/P{sub ohm} {gt} 10) are characterized as a peakedness parameter (F{sub ne} = n{sub eo}/{l angle}n{sub e}{r angle}) in the Tokamak Fusion Test Reactor (TFTR). The gross energy confinement time ({tau}{sub E} = E{sub tot}/P{sub tot}) at the time of maximum stored energy is found to be a weak function of the plasma current and total heating power but depends strongly on the peakedness parameter. A regression study showed {tau}{sub E} = 2.4 {times} 10{sup {minus}3}F{sub ne}{sup 0.76}I{sub P}{sup 0.18}P{sub tot}{sup {minus}0.12} for a data set of 561 discharges in the TFTR. Also {tau}{sub E} can be represented as {tau}{sub E} = {tau}{sub E}{sup L}f(F{sub ne}), where {tau}{sub E}{sup L} is the empirical L-mode scaling result. A similar scaling applies to an appropriately defined incremental energy confinement time ({tau}{sub inc} = dE{sub tot}/dP{sub tot}{vert bar}{sub F{sub ne} = constant}). 14 refs., 4 figs.

Progress in the neutral beam injection heating experiment on the Tokamak fusion test reactor

Abstract: The principal heating system for the Tokamak Fusion Test Reactor (TFTR) consists of four beamlines to inject beams of neutral deuterium into the tokamak plasma. We have recently injected beams at total powers up to about 30 MW, and we have achieved ion temperatures in the plasma core of 30 keV and more.

Kinetic Facial Selectivity in Nucleophilic Displacements at Tetracoordinate Phosphorus: Kinetics and Stereochemistry in the Reaction of Sodium Ethoxide with O,S-Dimethyl Phenylphosphonothioate.

Abstract: Les auteurs demontrent que le deplacement de l'ion methylthiolate du thiophosphonate du titre, par l'ion ethanolate s'effectue avec une inversion complete de configuration du phosphore