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Biomedical subjects

D L Turner

Publications and source records attributed to D L Turner.

At least 91 records · Page 5Linked to original sources
PubMed1992

Regulation of perfusive O2 transport during exercise in humans: effects of changes in haemoglobin concentration.

1. Recently it was suggested that submaximal cardiac output (Q) could vary in response to changes in arterial O2 concentration (Ca,O2), so that arterial O2 delivery (Qa,O2 = Q x Ca,O2, in ml min-1) is kept constant. 2. This hypothesis was tested on eight healthy male subjects, at rest and during exercise (50, 100 and 150 W) in three conditions: normaemia (N), after 6 weeks of endurance training (T), and 2 days after subsequent autologous blood reinfusion (P). 3. Measured variables were oxygen consumption (VO2), by open circuit method, Q, by a CO2 rebreathing method, and haemoglobin concentration ([Hb]), by a photometric method. Ca,O2 was calculated as the product of [Hb], arterial O2 saturation (0.97), and the O2 binding coefficient. 4. [Hb] and thus Ca,O2 increased by 2.6% (T vs. N) and subsequently by further 5.8% (P vs. T). VO2 and Qa,O2 were linear functions of power (w), both relationships being unaffected by changes in Ca,O2. As a consequence, the linear Q vs. VO2 relationships were shifted downward as Ca,O2 increased. 5. The VO2 vs. w and the Qa,O2 vs. w relationships had the same slope. Therefore, the difference between Qa,O2 (w) and VO2 (w), equal to O2 flow in mixed venous blood (Qv,O2), was constant. 6. In conclusion, the tested hypothesis was supported by the present results. The observed constancy of Qv,O2 suggested that Qv,O2 may play a key role in regulating the cardiovascular response to exercise.

Adult↗
PubMed1991

Synthesis, conformational properties, and antibody recognition of peptides containing beta-turn mimetics based on alpha-alkylproline derivatives.

Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a beta-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the beta-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic gamma-lactam bridge between the alpha-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-alpha-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stabilized relative to that in the native sequence. For the (S)-alpha-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the gamma-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-alpha-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.

Amino Acid Sequence↗
PubMed1991

Cardiovascular and respiratory control mechanisms during exercise: an integrated view.

Exercise can impose an immense stress upon many physiological systems throughout the body. In order that exercise performance may be optimally maintained, it is essential that a profound and complex series of responses is coordinated and controlled. The primary site for coordination is the central nervous system, whereas control mechanisms (both feedback loops and feedforward activation) involve complex sensory information, often in the form of neural coding but also in the form of blood-borne chemical signals, a number of levels of peripheral and central integration and, finally, the efferent branches of the nervous system coursing via sympathetic and parasympathetic nerves to target sites of action. The neurohumoral control of the cardiorespiratory responses to exercise has received intense attention for over two decades and some particularly important steps forward in its understanding have occurred within the last 10 years. The initial fast increase (phase 1) in cardiovascular and ventilatory flow parameters are brought about by neurally mediated muscle mechanoreceptor feedback reflexes and a feedforward 'central motor command'. The blood pressure operating point is also raised by a combination of these two neural mechanisms. Fine control of the matching of cardiac output to ventilation may occur by means of a feedforward ventilatory control of cardiac origin. During the slower phase of adjustment (phase 2), the neurally mediated mechanisms are augmented by a cohort of humorally mediated feedback reflexes involving muscle and vascular chemoreceptors as well as being supported by central neural reverberation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cytochrome c'' isolated from Methylophilus methylotrophus. An example of bis-histidine-co-ordinated Fe3+ haem, with near-perpendicular orientation of the ligands.

Cytochrome c'' (Methylophilus methylotrophus) is a soluble protein, Mr 15,000, possessing one haem which is high-spin in the reduced state but switches to a low-spin form on oxidation. Low-temperature electron-paramagnetic-resonance spectroscopy of the oxidized state shows a low-spin signal at gz = 3.65 with a folded line-shape typical of a haem of low rhombicity, and the near-infrared magnetic-circular-dichroism (m.c.d.) spectra reveal an unusually intense (delta epsilon = 400 M-1.cm-1 at 5 T, 4.2 K) charge-transfer band at 1560 nm, establishing that the oxidized haem is co-ordinated by two His residues in a near-perpendicular orientation. This conformation is well established for transmembrane b cytochromes, but this appears to be the first example in a water-soluble cytochrome. The low-temperature m.c.d. spectra of the reduced form of the protein confirms that the haem contains a high-spin Fe2+ ligated by one His residue. The redox-linked spin-state change releases a His group. Since this residue is likely to bind a proton at pH values less than 6.5, this cytochrome may provide a useful model of a molecular mechanism of a redox-linked proton uptake and release process.

Bacteria↗
PubMed1990

The protein Id: a negative regulator of helix-loop-helix DNA binding proteins.

We have isolated a cDNA clone encoding a novel helix-loop-helix (HLH) protein, Id. Id is missing the basic region adjacent to the HLH domain that is essential for specific DNA binding in another HLH protein, MyoD. An in vitro translation product of Id can associate specifically with at least three HLH proteins (MyoD, E12, and E47) and attenuate their ability to bind DNA as homodimeric or heterodimeric complexes. Id is expressed at varying levels in all cell lines tested. In three cell lines that can be induced to undergo terminal differentiation, Id RNA levels decrease upon induction. Transfection experiments indicate that over-expression of Id inhibits the trans-activation of the muscle creatine kinase enhancer by MyoD. Based on these findings, we propose that HLH proteins lacking a basic region may negatively regulate other HLH proteins through the formation of nonfunctional heterodimeric complexes.

Amino Acid Sequence↗
PubMed1990

Lineage-independent determination of cell type in the embryonic mouse retina.

We previously used a retroviral vector to mark clones in the postnatal rodent retina and showed that at least two types of neurons and Müller glia can arise from a common progenitor. Here we describe the use of exo utero surgery to introduce a marker retrovirus into the proliferative zone of the retinas of embryonic day 13 and 14 mice. Analysis of marked clones in the resulting adult retinas shows that almost all progenitor cells that continued mitosis were multipotential and that a single progenitor can generate most retinal cell types. The size of marked clones indicates that retinal cells do not employ a stem cell mode of division, but instead, both daughter cells of a progenitor can continue to divide. These results suggest that cell type determination in the rodent retina is independent of lineage. We propose a model for the generation of retinal cell types in which the cessation of mitosis and cell type determination are independent events, controlled by environmental interactions.

Animals↗
PubMed1988

31P nuclear magnetic resonance measurement of free erythrocyte magnesium concentration in man and its relation to blood pressure.

1. 31P n.m.r. spectroscopy was used to measure the dissociation constant of MgATP under simulated intracellular conditions and to measure erythrocyte free magnesium concentration. 2. In a group of 40 subjects, the relationship between erythrocyte free magnesium and blood pressure, age and sex was examined by univariate and multivariate regression analysis. 3. A weak positive association was found between erythrocyte free magnesium and mean blood pressure. This association was lost in a multivariate regression analysis including both age and sex. 4. No significant relationship was found between erythrocyte free magnesium and age, sex, family history of hypertension or use of the combined oral contraceptive pill in the sample studied.

Adult↗
PubMed1988

Effect of training on maximal oxygen uptake and aerobic capacity of locomotory muscles in tufted ducks, Aythya fuligula.

1. The effects of artificial swim training on maximal oxygen consumption and heart rate, as well as on the capillarity and oxidative capacity of locomotory muscles, have been studied in the tufted duck, Aythya fuligula. 2. The artificial training programme resulted in a 27% increase in maximal oxygen consumption, mainly as a result of an increase in muscle capillarity (20% increase in capillary/fibre ratio). In addition, activity of an oxidative enzyme, citrate synthase, increased (by 42%) and there was a significant transformation of fibre types in the lateral gastrocnemius muscle. 3. Altering the duration and nature of the training stimulus, for example flying and diving, can bring about different degrees of muscular adaptation, particularly in oxidative capacity.

Adaptation, Physiological↗
PubMed1988

The aerobic capacity of locomotory muscles in the tufted duck, Aythya fuligula.

The locomotory muscles of the tufted duck, Aythya fuligula (L.), were analysed for mass, aerobic and anaerobic enzyme activities, fibre-type proportions, capillarity, mitochondrial and myoglobin content. The estimated aerobic capacity of the muscles correlated well with the muscles' maximal oxygen uptake both when measured during swimming and when predicted for steady-state flight. The results suggest that exercise performance in birds cannot be predicted purely on the basis of muscle mass (see Butler & Woakes, 1985); the specific enzyme complement of each muscle must also be taken into account. The delivery of oxygen to mitochondria is facilitated by the dense capillarity and high myoglobin content of the muscles.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1988

Regional distribution of blood flow during swimming in the tufted duck (Aythya fuligula).

The distribution of blood flow to a number of organs and tissues of the tufted duck was determined (by the microsphere technique) before and while the birds were swimming at close to their maximum sustainable velocity (i.e. at 0.69 +/- 0.01 ms-1). During swimming, oxygen uptake was twice the pre-exercise value. Cardiac output increased by 70%, there was no significant change in arterial blood pressure and total systemic conductance increased by 44%. There were no significant changes in blood flow to the brain, liver, adrenal glands, spleen and respiratory muscles. Not surprisingly, there were increases in blood flow to the heart (30% increase) and to the muscles of the hindlimbs (to 3.1 times the pre-exercise value). Significant reductions in flow occurred to various parts of the gastrointestinal tract (although not to the gastrointestinal tract as a whole), to the pancreas and to the pectoralis muscles. In the case of the flight musculature as a whole, the reduction was to approximately 40% of the values in the ducks before exercise. Thus, despite the fact that cardiac output was some three times lower than it would have been during flight, there was a clear redistribution of blood away from some visceral organs and inactive muscles during surface swimming in the tufted duck. This lends support to the suggestion that blood is selectively directed to the legs, as well as to the brain and central nervous system (CNS) and away from the visceral organs and inactive muscles during voluntary diving in these birds.

Animals↗
PubMed1987

Proton NMR studies of horse ferricytochrome c. Completion of the assignment of the well resolved hyperfine shifted resonances.

1H NMR saturation transfer and nuclear Overhauser effect (NOE) measurements have been used together with two-dimensional spectra to complete the assignment of the well resolved hyperfine shifted resonances in the spectrum of horse ferricytochrome c and obtain their shifts in the reduced protein. New assignments include the beta-CH2 protons of Met-80, both ring protons of His-18, and the alpha-CH2 of Gly-29 and delta-CH2 of Pro-30, which resonate surprisingly far upfield despite the absence of any Fermi contact contribution to the shift.

Animals↗
PubMed1986

13C and proton NMR studies of horse cytochrome c. Assignment and temperature dependence of methyl resonances.

The 13C and proton chemical shifts of the 55 methyl groups of horse cytochrome c have been determined over a range of temperatures both in the diamagnetic ferrocytochrome and in the paramagnetic ferricytochrome. Specific assignments of many proton resonances have been published previously and all of the remaining methyl proton resonances are now specifically assigned. The corresponding 13C assignments follow directly, including those of contact shifted 13C resonances which are reported for the first time.

Animals↗
PubMed1985

13C-NMR studies of horse ferrocytochrome c. Assignment and temperature dependence of methyl resonances.

The 13C and proton chemical shifts of 53 of the 55 methyl resonances of horse ferrocytochrome c have been determined by editing natural abundance 13C spectra according to the number of attached protons, observing the temperature dependence of the chemical shifts, and correlating 13C and proton chemical shifts in two-dimensional spectra. Previous assignments of proton shifts allow 16 of the 13C resonances to be assigned firmly.

Animals↗
PubMed1982

The therapeutic community: a critical reappraisal.

Any new concept or movement can be understood only when considered in light of the sociopolitical context in which it emerges. The authors critically assess the concept of the therapeutic community in such terms. They assert that the therapeutic community should be viewed as a protest movement itself, or as part of a greater protest against the dehumanizing conditions of mental hospitals in the early 20th century. As a protest movement it has achieved significant success. However, the author say, its therapeutic value has yet to be conclusively demonstrated and its practicability is also highly questionable. The authors suggest that the therapeutic community should be reassessed in light of changed social conditions, and a new and more pragmatic approach to organizing psychiatric hospitals be formulated.

Humans↗