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Biomedical subjects

A H Anderson

Publications and source records attributed to A H Anderson.

17 recordsLinked to original sources

The effects of multimedia communication technology on non-collocated teams: a case study.

Collaborative teams are becoming increasingly important for industry, both within and across companies. There is a need for communication technology to support teams because many teams are non-collocated, or 'virtual'. Two automotive supply chain teams were observed while they were experimenting with multimedia conferencing in order to determine what support non-collocated teams need and the potential effects of introducing technologies on their group processes. The observations included meeting recordings and other sources that show the organizational factors affecting teams. Working in teams requires very close collaboration. Communication technology can help teams if it is used to foster close and relatively informal person-to-person interaction. Organizational constraints on how the technology is introduced favour high-technology, special-purpose installations, but teams can best be supported using relatively modest equipment with desktop access.

Ergonomics↗

Studies on the monoamine oxidase-B-catalyzed biotransformation of 4-azaaryl-1-methyl-1,2,3,6-tetrahydropyridine derivatives.

The substrate properties of a series of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridinyl (MPTP) analogues in which the C-4 phenyl group has been replaced with various 4-azaaryl moieties have been examined in an effort to evaluate the contribution of electronic, polar, and steric parameters to the MAO-B-catalyzed oxidation of this type of cyclic tertiary allylamine to the corresponding dihydropyridinium metabolite. No significant correlation could be found with the calculated energy of the C-H bond undergoing cleavage. A general trend, however, was observed between the magnitude of the log P value with the magnitude of kcat/Km. The results indicate that the placement of a polar nitrogen atom in the space occupied by the phenyl group of MPTP leads to a dramatic decrease in substrate properties. Enhanced substrate properties, however, were observed when benzoazaarenes replaced the corresponding five-membered azaarenes. These results are consistent with our previously published molecular model of the active site of MAO-B.

Animals↗

Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition.

BACKGROUND: Protein intake is frequently delayed in ill neonates because of concerns about their ability to metabolize substrates. OBJECTIVE: We aimed to determine the factors affecting protein balance in ventilated, parenterally fed newborns during the first week of life. DESIGN: Leucine kinetic studies were performed in 19 neonates by using the [1-(13)C]leucine tracer technique after 24 h of a stable total parenteral nutrition (TPN) regimen. TPN intakes were prescribed by rotating attending physicians, enabling assessment of protein metabolism over a range of clinically used nutrient intakes. RESULTS: Mean (+/-SD) birth weight was 1.497 +/- 0.779 kg, gestational age at birth was 30.3 +/- 4.0 wk, and age at study was 3.9 +/- 1.4 d. Amino acid intakes (AAIs) ranged from 0.0 to 2.9 g x kg(-1) x d(-1). Based on leucine kinetic data, protein balance was calculated as the difference between protein synthesis and catabolism. By multiple regression analysis, AAI was the only predictor associated independently with protein balance (P < 0.01); energy intake, lipid intake, glucose intake, birth weight, and gestational age were not. Both leucine oxidation and nonoxidative leucine disposal rates were significantly correlated with leucine intake (P < 0.0005 and P < 0.01, respectively). Of the 12 infants with AAIs > 1 g x kg(-1) x d(-1), only 1 infant was significantly catabolic (protein balance <-1 g x kg(-1) x d(-1)). There was no evidence of protein intolerance as determined by elevated creatinine (69 +/- 31 micromol/L), plasma urea nitrogen (6.7 +/- 2.53 mmol/L), or metabolic acidosis (pH: 7.36 +/- 0.05). CONCLUSIONS: Ill neonates can achieve a positive protein balance in the first days of life without laboratory evidence of protein toxicity.

Amino Acids↗

Placental transport of threonine and its utilization in the normal and growth-restricted fetus.

Placental transport and fetoplacental utilization of threonine (Thr) were compared at 130 +/- 1 days gestational age between seven control ewes (C) and six ewes in which intrauterine growth restriction (IUGR) had been induced by exposure to high ambient temperature from 33 +/- 1 to 112 +/- 2 days of gestation. The fluxes were measured using simultaneous intravenous infusions of L-[1-13C]Thr into the mother and L-[U-14C]Thr into the fetus. The IUGR group had less fetal weight (1.27 +/- 0.14 vs. 3.10 +/- 0.10 kg, P < 0.01) and placental weight (120 +/- 17 vs. 295 +/- 14 g, P < 0.01) than the C group. The direct flux of maternal Thr into the fetal systemic circulation was less in the IUGR fetuses, both relative to fetal weight (1.40 +/- 0.19 vs. 2.19 +/- 0.18 mumol.min-1.kg fetus-1, P = 0.0107) and placental weight (1.5 +/- 0.2 vs. 2.3 +/- 0.2 mumol.min-1.100 g placenta-1, P = 0.0187). In both groups, there was excretion of CO2 produced from fetal Thr. The rate of CO2 production from fetal plasma Thr carbon by fetus plus placenta was reduced in the IUGR group (1.50 +/- 0.23 vs. 2.86 +/- 0.32 mumol.min-1.kg fetus-1, P = 0.0065). We conclude that the flux of maternal Thr into the IUGR fetus is markedly reduced because of a reduction in placental mass and because of a weight-specific reduction in Thr placental transport. The reduced flux is routed into fetal Thr accretion via a decrease in fetal Thr oxidation.

Animals↗

Limited visual control of the intelligibility of speech in face-to-face dialogue.

Speakers are thought to articulate individual words in running speech less carefully whenever additional nonacoustic information can help listeners recognize what is said (Fowler & Housum, 1987; Lieberman, 1963). Comparing single words excerpted from spontaneous dialogues and control tokens of the same words read by the same speakers in lists, Experiment 1 yielded a significant but general effect of visual context: Tokens introducing 71 new entities in dialogues in which participants could see one another's faces were more degraded (less intelligible to 54 naive listeners) than were tokens of the same words from dialogues with sight lines blocked. Loss of clarity was not keyed to moment-to-moment visual behavior. Subjects with clear sight lines looked at each other too rarely to account for the observed effect. Experiment 2 revealed that tokens of 60 words uttered while subjects were looking at each other were significantly less degraded (in length and in intelligibility to 72 subjects) vis-à-vis controls than were spontaneous tokens of the same words produced when subjects were looking elsewhere. Intelligibility loss was mitigated only when listeners looked at speakers. Two separate visual effects are discussed, one of the global availability and the other of the local use of the interlocutor's face.

Adult↗

Deuterium isotope effect studies on the MAO-B catalyzed oxidation of 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine.

Previous studies have established that 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine is an efficient time- and concentration-dependent inhibitor of the flavin-containing enzyme monoamine oxidase B (MAO-B). This behavior is consistent with a proposed mechanism-based inactivation pathway which proceeds via an initial single electron transfer step to generate an unstable cyclopropylaminyl radical cation intermediate that alkylates an active site functionality via the ring opened primary carbon centered radical. More recently we have found that, in addition to being an inhibitor, the corresponding 1-cyclopropyl-4-benzyl-1,2,3,6-tetrahydropyridine species is an excellent MAO-B substrate, behavior which may not be consistent with the obligatory formation of a cyclopropylaminyl radical cation intermediate. In an attempt to gain further insight into the mechanism associated with the MAO catalyzed oxidation of 1,4-disubstituted tetrahydropyridines, we have undertaken deuterium isotope effect studies on the substrate and inhibitor properties of this 4-benzyl-1-cyclopropyltetrahydropyridine derivative. A normal isotope effect was observed on kcat/KM. Although the good substrate properties of this compound prevented an accurate estimate of k(inact) and K1, we did observe a very modest inverse isotope effect on the rate of inactivation of 0.1 microM MAO-B by 500 microM inactivator. The results are discussed in terms of possible mechanisms for the MAO-B catalyzed oxidation of 1,4-disubstituted 1,2,3,6-tetrahydropyridines.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Synthesis and monoamine oxidase B catalyzed oxidation of C-4 heteroaromatic substituted 1,2,3,6-tetrahydropyridine derivatives.

The monoamine oxidase B (MAO-B) catalyzed oxidation of amines has been proposed to proceed via a polar pathway, an initial single-electron transfer pathway and an initial hydrogen atom transfer pathway. Results from previous studies on selected N-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridine derivatives have led us to consider a mechanism for these cyclic tertiary allylamines which may not necessarily involve the aminyl radical cation as required by an initial single-electron transfer step. The studies summarized in this paper were undertaken to explore further the structural features that determine the MAO-B substrate and/or inactivator properties of various 1,4-disubstituted tetrahydropyridine derivatives. We report here the results of our studies on the synthesis and MAO-B catalyzed oxidation of 1-methyl- and 1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives bearing a variety of heteroaromatic groups at C-4. All of the N-cyclopropyltetrahydropyridine analogs were time and concentration dependent inhibitors of MAO-B while all of the N-methyltetrahydropyridine analogs and the N-cyclopropyl-4-(1-methyl-2-pyrryl)tetrahydropyridine analog were substrates. The substrate properties (Kcat/KM) covered a range of 6 to 1800 min-1 mM-1 while the range for the inactivator properties for which Kinact/KI values could be obtained was 0.1-1.0 min-1 mM-1. The partition ratios for the N-cyclopropyl analogs varied from 4 to 17 except for the 4-(1-methyl-2-pyrryl) analog, which had a partition ratio of 400. These results are discussed in terms of the putative allylic radical intermediate and in the context of the hydrogen atom transfer and single-electron transfer based mechanisms.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Interactive communication between children: learning how to make language work in dialogue.

In this paper we investigate the development of interactive communication skills in 170 children aged seven to thirteen. Using a communication task that allows extended dialogues between pairs of young speakers, we are able to assess both the overall communicative success achieved by any pair; and from an analysis of the dialogues we can identify several interactive strategies that characterize older and more successful communicators. Successful communication involves the active involvement of both participants: asking and answering questions, volunteering information and responding sensitively to contributions from their partners. In contrast to the process of language acquisition, the development of these interactive skills takes place over an extended time period and subjects vary greatly in their ability to communicate effectively. For many analyses differences in the communicative success achieved by subjects differ more within than between age groups. For example, a substantial minority of our oldest subjects communicate no better than children six years younger.

Adolescent↗

The unintelligibility of speech to children: effects of referent availability.

Speech addressed to children is supposed to be helpfully redundant, but redundant or predictable words addressed to adults tend to lose intelligibility. Word tokens extracted from the spontaneous speech of the parents of 12 children aged 1; 10 to 3; 0 and presented in isolation to adult listeners showed loss of intelligibility when the words were redundant because they had occurred in repetitions of an utterance (Experiment 1) or referred to an entity which was physically present when named (Experiment 2). Though children (N = 64; mean age 3; 5, S.D. 6.1 months) recognized fewer excerpted object names than adults (N = 40), less intelligible tokens appeared to induce child listeners to rely on the word's extra-linguistic context during the recognition process (Experiment 3), much as such tokens normally induce adults to rely on discourse context. It is proposed that interpreting parental utterances with reference to non-verbal context furthers linguistic development.

Adult↗

Systemic hypertension in infants with severe bronchopulmonary dysplasia: associated clinical factors.

The clinical course of 87 infants with bronchopulmonary dysplasia (BPD) on home oxygen therapy was reviewed to determine the occurrence of systemic hypertension (HTN) and to evaluate associated clinical features. Eleven of 87 (13%) infants developed systemic HTN either in the neonatal intensive care unit or following discharge. Clinical features that distinguished the hypertensive from the normotensive group were as follows: greater use of bronchodilators, 91% vs 37% (p < 0.001), and diuretics, 91% vs 55% (p < 0.05), longer duration of home oxygen therapy 21.6 +/- 9.9 vs 9.2 +/- 5.8 months (p < 0.05), and greater mortality, 36% vs 1% (p < 0.001). The course of systemic HTN in the surviving patients (7 of 11) was benign and resolved in all patients prior to weaning from home oxygen therapy. Systemic HTN is frequently present in infants with severe BPD and appears to be related to the clinical severity of lung disease.

Bronchopulmonary Dysplasia↗

The Human Communication Research Centre dialogue database.

The HCRC dialogue database consists of over 700 transcribed and coded dialogues from pairs of speakers aged from seven to fourteen. The speakers are recorded while tackling co-operative problem-solving tasks and the same pairs of speakers are recorded over two years tackling 10 different versions of our two tasks. In addition there are over 200 dialogues recorded between pairs of undergraduate speakers engaged on versions of the same tasks. Access to the database, and to its accompanying custom-built search software, is available electronically over the JANET system by contacting liz@psy.glasgow.ac.uk, from whom further information about the database and a user's guide to the database can be obtained.

Adolescent↗

Studies of the topoisomerase II-mediated cleavage and religation reactions by use of a suicidal double-stranded DNA substrate.

The cleavage and religation reactions of eukaryotic topoisomerase II were studied by use of a 5'-recessed DNA substrate containing a strong recognition sequence for the enzyme. Cleavage of the DNA substrate was suicidal, that is the enzyme was unable to religate the cleaved DNA due to a release of DNA 5' to the cleavage position. With this substrate cleavage products accumulated with time in the absence of protein-denaturing agents, and the cleavage reaction was not reversible with salt. The suicide cleavage complexes contained a kinetically competent topoisomerase II enzyme as determined by the enzyme's ability to perform intermolecular ligation of the cleaved DNA to a free 3'-hydroxyl end on another DNA strand. The efficiency of the religation reaction depended on the ability of the religation substrate to base pair to the DNA in the cleaved enzyme-DNA complex. Higher levels of religation were obtained with dinucleotides than with long DNA substrates. Mononucleotides also were efficiently religated, indicating an ability of the enzyme to mediate religation without making contacts to a long stretch of nucleotides 5' to the cleavage position.

Animals↗

Introducing information in dialogues: forms of introduction chosen by young speakers and the responses elicited from young listeners.

Young speakers in dialogue must establish mutual knowledge. Traditionally, researchers have focused on how children used indefinite and definite articles to signal novel and shared information. In this study of 170 children aged seven to thirteen, the form of introduction chosen, whether question or statement, is more significant than the type of article used. No developmental effects on article use emerge, with statement + indefinite always the least common choice. However, young speakers use question introductions significantly less than older children. There is also a developmental interaction between speakers' and listeners' behaviour. Question introduction elicit effective listener responses at all ages, but only twelve-year-olds respond reliably to statements. Unfortunately, young speakers prefer just those forms of introduction to which young listeners are least likely to provide informative feedback. Thus two separate developmental effects appear to combine to hamper young subjects' chances of achieving successful communication in dialogues.

Age Factors↗

Probing the mechanism of bioactivation of MPTP type analogs by monoamine oxidase B: structure-activity studies on substituted 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridines.

Previous studies have shown that 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine is an excellent monoamine oxidase B (MAO-B) substrate (kappa cat/KM = 1538 min-1 mM-1) although the corresponding 4-phenyl analog displays MAO-B inactivating properties only. This behavior led us to speculate that the pathway for the MAO-B catalyzed oxidation of these tetrahydropyridines may not necessarily proceed via an initial single electron transfer step as proposed by others but rather through an initial alpha-carbon hydrogen atom abstraction step. In the present studies we have examined the interactions of various 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives, some of which bear substituents on the phenyl ring. The 4-thiophenoxy- and all of the 4-phenoxytetrahydropyridine derivatives proved to be substrates but not inactivators of MAO-B, while several of the 4-phenyltetrahydropyridine derivatives were inactivators but not substrates. A case of particular interest was 1-cyclopropyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine, which displayed only substrate properties. The results are discussed in terms of two catalytic pathways, one of which involves partitioning of the proposed cyclopropylaminyl radical cation intermediate between cyclopropyl ring opening and proton loss while the second involves partitioning of the parent amine between an initial single electron transfer step, leading to cyclopropylaminyl radical cation formation and enzyme inactivation, and an initial alpha-carbon hydrogen atom abstraction step, leading to an allylic radical and dihydropyridinium product formation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗