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Biomedical subjects

N A Taylor

Publications and source records attributed to N A Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Sequence requirements for processing of proinsulin in transfected mouse pituitary AtT20 cells.

To investigate the sequence requirements for proteolytic processing of prohormones at pairs of basic amino acids, normal and mutant proinsulins were expressed in the mouse pituitary corticotrophic cell line AtT20. The extent of processing was determined by h.p.l.c. analysis of insulin-like immunoreactivity secreted into the media of transfected cells. In this model system, normal proinsulin was efficiently processed to insulin. The mutant des-38-62-proinsulin, in which all but six amino acids of the C-peptide were deleted, was also processed to insulin but less efficiently than the wild-type. The mutant Lys64-Arg65 to Thr64-Arg65 was partially processed to insulin, while the mutant Arg31-Arg32 to Arg31-Gly32 was not processed at either site. These results indicate: (i) that a six-amino-acid spacer between the two pairs of basic amino acids in proinsulin is sufficient to permit processing at both sites; (ii) that the endoproteinase responsible for cleavage at the Lys64-Arg65 site will also recognize Thr64-Arg65; (iii) that the endoproteinase responsible for cleavage at the Arg31-Arg32 site will not recognize Arg31-Gly32; and (iv) that the change Arg31-Arg32 to Arg31-Gly32 affects processing at the Lys64-Arg65 site.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Functional torque-velocity and power-velocity characteristics of elite athletes.

Technical limitations of some isokinetic dynamometers have called into question the validity of some data on human muscle mechanics. The Biodex dynamometer has been shown to minimize the impact artefact while permitting automatic gravity correction. This dynamometer was used to study quadriceps muscle torque and power generation in elite power (n = 6) and elite endurance (n = 7) athletes over 12 randomly assigned isokinetic velocities from 30 degrees.s-1 to 300 degrees.s-1. The angle at peak torque varied as a negative, linear function of angular velocity, with the average angle across test velocities being 59.5 degrees (SD 10.2 degrees). Power athletes developed greater peak torque at each angular velocity (P less than 0.05) and experienced a 39.7% decrement in torque over the velocity range tested. Endurance athletes encountered a 38.8% decline in peak torque. Torques measured at 60 degrees of knee flexion followed a similar trend in both groups; however the greatest torques were recorded at 60 degrees.s-1 rather than at 30 degrees.s-1. Leg extensor muscle power increased monotonically with angular velocity in both power (r2 = 0.728) and endurance athletes (r2 = 0.839); however these curves diverged significantly so that the power athletes produced progressively more power with each velocity increment. These inter group differences probably reflected a combination of natural selection and training adaptation.

Adult↗
PubMed1991

Lung volume changes in response to altered breathing gas pressure during upright immersion.

Since elastic and flow-resistive respiratory work are volume dependent, changes in lung volume during immersion affect respiratory effort. This investigation examined changes in lung volume with air delivery pressure modifications during upright immersion. Static pressure-volume relaxation relationships and lung volumes were obtained from ten immersed subjects breathing air at four delivery pressures: mouth pressure, lung centroid pressure (PLC), and 0.98 kPa above and below PLC. The PLC is the static lung pressure which returns the respiratory relaxation volume (VR) to normal and was previously determined to be +1.33 kPa relative to pressure at the sternal notch. Lung volume changes observed when breathing air at mouth pressure were reversed when air was supplied at PLC. The expiratory reserve volume (ERV) and VR were reduced by 58% and 87%, respectively, during uncompensated immersion. These differences indicated an active defence of ERV and implied that additional static respiratory work was required to overcome transrespiratory pressure gradients.

Adult↗
PubMed1991

Static and dynamic assessment of the Biodex dynamometer.

The validity and accuracy of the Biodex dynamometer was investigated under static and dynamic conditions. Static torque and angular position output correlated well with externally derived data (r = 0.998 and r greater than 0.999, respectively). Three subjects performed maximal voluntary knee extensions and flexions at angular velocities from 60 to 450 degrees.s-1. Using linear accelerometry, high speed filming and Biodex software, data were collected for lever arm angular velocity and linear accelerations, and subject generated torque. Analysis of synchronized angular position and velocity changes revealed the dynamometer controlled angular velocity of the lever arm to within 3.5% of the preset value. Small transient velocity overshoots were apparent on reaching the set velocity. High frequency torque artefacts were observed at all test velocities, but most noticeably at the faster speeds, and were associated with lever arm accelerations accompanying directional changes, application of resistive torques by the dynamometer, and limb instability. Isokinematic torques collected from ten subjects (240, 300 and 400 degrees.s-1) identified possible errors associated with reporting knee extension torques at 30 degrees of flexion. As a result of tissue and padding compliance, leg extension angular velocity exceeded lever arm angular velocity over most of the range of motion, while during flexion this compliance meant that knee and lever arm angles were not always identical, particularly at the start of motion. Nevertheless, the Biodex dynamometer was found to be both a valid and an accurate research tool; however, caution must be exercised when interpreting and ascribing torques and angular velocities to the limb producing motion.

Adolescent↗
PubMed1991

Pulmonary flow-resistive work during hydrostatic loading.

This paper focuses upon flow-resistive pulmonary work during upright immersion, and during changes in the air delivery pressure. Nine male non-smokers (aged 26.2 +/- 3.5 years), with normal lung function history, performed spontaneous respiration while seated in air (control) and during total immersion. During the immersed state subjects were supplied with air at four hydrostatic pressures: mouth pressure (PM; simulating a mouth-held demand regulator), lung centroid pressure (PLC; + 1.33 kPa relative to the sternal notch), and 0.98 kPa (10 cmH2O) above and below the lung centroid pressure. Inspiratory, expiratory and total flow-resistive pulmonary work were computed from the integration of transpulmonary pressure (difference between oesophageal and mouth pressure) with respect to lung volume change. When breathing air delivered at mouth pressure, immersion significantly elevated all total flow-resistive pulmonary work components (P less than 0.05). Each increment in breathing pressure resulted in a progressive reduction in expiratory and total flow-resistive pulmonary work, so that when air was provided at lung centroid pressure and lung centroid pressure +0.98 kPa both components were similar to control values (P greater than 0.05). Inspiratory was always less than expiratory pulmonary work. During immersion inspiratory pulmonary work was significantly reduced when air supply pressure was increased above mouth pressure (P less than 0.05). Subsequent pressure increments failed to produce further changes in inspiratory pulmonary work. The difference in response between the inspiratory and expiratory components of total flow resistive pulmonary work was attributed primarily to the volume-dependence of the expiratory component.

Adult↗
PubMed1990

Serotonin antagonism reduces the adverse symptoms of beta blockade.

Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line treatment for hypertension, but they have been associated with unwanted symptoms including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin S2-receptor antagonist that has previously been shown to reduce blood pressure in hypertensive patients by reducing systemic vascular resistance. Hypertensive patients whose sitting diastolic blood pressure was greater than or equal to 95 mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were selected for the study. The beta-blocker dose remained constant throughout the study, but patients were randomly allocated to receive ketanserin 20 mg twice daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus placebo at night in addition to the beta-blocker therapy. One hundred and forty two patients completed the symptom questionnaire at randomization and after 12 weeks treatment. The treatment groups were well matched for age, sex, weight, and blood pressure. Blood pressure was reduced significantly by all treatments, and there were no between-group differences. Bendrofluazide adversely affected alertness (p less than 0.05) and concentration (p less than 0.01) whereas ketanserin had no significant effect and the ketanserin 20 mg twice daily group had better concentration than the bendrofluazide group (p less than 0.05). Ketanserin treatment reduced the incidence of nightmares (p less than 0.05 for 20 mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide treatment in this respect (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

Three-dimensional surfaces for human muscle kinetics.

Torque, angular velocity and angular position data were collected on six subjects performing maximum knee extensions at 11 speeds. Three-dimensional (3-D) surfaces were drawn for each subject and for the normalised, averaged data. For each subject, the moment arms of knee extensor and patella excursion were determined from radiographs and averaged across subjects. These data were then used to convert the angular data to linear force, velocity and information on muscle length. Surfaces were plotted for these data and evaluated. Results indicate a major difference between the knee positions for production of peak force or torque. Peak linear force was found to occur at an average of 75 degrees of flexion, while peak torque was found at 57 degrees. It was also suggested that 3-D surfaces provide more information than the traditional methods of presenting dynamic strength results.

Adult↗
PubMed1990

Computer integrated measurement of respiratory compliance.

Respiratory compliance is obtained from the ratio of lung volume change to change in differential pressure across the chest wall, and is classically derived from the slope of the static, transrespiratory pressure-volume relationship. The need to remove subjectivity from the derivation of respiratory compliance, has prompted the development of a computer-based system which facilitates compliance measurement with minimal experimenter error. This paper outlines the basic algorithms necessary to analyse static, quasi-static and dynamic pressure-volume data, and describes how these data may be entered into a graphics package (Sigmaplot) to derive best-fit polynomial curves.

Algorithms↗
PubMed1990

Effects of breathing-gas pressure on pulmonary function and work capacity during immersion.

Upright immersion induces respiratory mechanical changes that may impair pulmonary function during hyperbaric exercise. To evaluate this, 10 divers performed an incremental cycling protocol while immersed upright at 1.02 and 6.05 atmospheres absolute (atm abs). Air was supplied at each of two hydrostatic pressures: mouth pressure (Pm: to stimulate a mouth-held demand regulator) and lung centroid pressure (PLC). Subjects perceived air delivery at PLC to be more comfortable at each level of exercise at both absolute pressures (P less than 0.05). At 6.05 atm abs subjects perceived narcosis to be greater for Pm than for PLC air delivery. Hypoventilation was encountered at 6.05 atm abs with PLC air delivery and was further exacerbated when air was delivered at Pm (P less than 0.05). It was concluded that hypoventilation and narcosis are reduced whereas respiratory comfort is increased when air is delivered at PLC. This change is possibly due to improved pulmonary mechanics accompanying PLC air supply pressure.

Adult↗
PubMed1990

Measurement of static and dynamic pulmonary work during pressure breathing.

Various environments alter static and flow-resistive pulmonary mechanics. Of interest to diving physiologists is the negative pressure breathing induced during upright immersions without appropriate modification of air supply pressure. This paper outlines methodologic considerations for determining static and flow-resistive pulmonary work under such exposures. Ten males performed inspiratory pressure-volume relaxation maneuvers and spontaneous breathing in air, and during upright immersion with mouth pressure air supply. The immersed lung centroid pressure (PLC) was +1.19 kPa relative to the hydrostatic pressure at the sternal notch. Immersion elevated inspiratory static work from 0.36 to 1.74 J.liter-1 (P less than 0.05). Pulmonary flow-resistive work was elevated from 0.20 to 0.75 J.liter-1 (P less than 0.05), whereas pulmonary resistance, determined at 0.5 liter.sec-1, increased from 0.18 to 0.44 kPa.liter-1.sec (P less than 0.05). No significant changes in the iso-volume compliance of the lung tissue, chest wall, or total respiratory system were observed (P greater than 0.05). Results indicate that increases in the work of breathing are due to a combination of hydrostatic pressure imbalance, increased pulmonary resistance, and reduced end-expiratory total respiratory compliance.

Adult↗
PubMed1990

A screening programme for hypertension in general practice.

It is recommended that hypertensive patients with a diastolic blood pressure of 100 mmHg be treated. However, it has been proposed that only 50% of hypertensives are diagnosed, and of these, 50% are not treated. We therefore set out to identify hypertensive patients in our practice, who were then actively treated, some in a clinical trial of ketanserin. Of the 3,384 patients (1,667 males and 2,707 females) who were invited to our surgery for a blood pressure measurement, 2,606 patients (77%) attended. The overall prevalence of hypertension in the patients, aged 35-65 years was 2.9%. This prevalence increased with age: from 1.0% in the 35-44 year age group to 3.5% at 45-54 years, and 4.4% at 55-64 years. The mean systolic but not diastolic blood pressure increased with age. There were more male hypertensives than females, except over 55 years of age. Of the 84 hypertensives identified after one visit, the majority remained hypertensive after an additional visit, and 31 agreed to participate in a clinical trial. After a four-week placebo run-in, 22 patients had a diastolic blood pressure above 95 mmHg and were randomly allocated to receive ketanserin 40 mg twice daily or metoprolol 100 mg twice daily. Treatment continued double-blind for three months. There were no significant differences in blood pressure reduction between the treatment groups. The heart rate was reduced more by metoprolol. There were no withdrawals for side effects and no major differences in subjective complaints between the two treatment groups.

Adult↗
PubMed1989

Proinsulin endopeptidase substrate specificities defined by site-directed mutagenesis of proinsulin.

Two endopeptidases are involved in the conversion of proinsulin; a type I activity directed at the B chain, Arg31,Arg32, C-peptide junction, and type II which cleaves the C-peptide, Lys64,Arg65, A chain junction. To define further the substrate specificities of these enzymes, a series of mutant preproinsulin cDNAs were generated by site-directed and deletion mutagenesis. These were inserted into pT7 plasmids and capped cRNA transcripts synthesized, that were then microinjected into Xenopus oocytes. Oocytes were biosynthetically radiolabeled with [3H]leucine and the secreted peptides (greater than 95% present as unprocessed proinsulins) then incubated with types I and II endopeptidase activities prepared from isolated insulinoma secretory granules. The reaction products were analyzed by high performance liquid chromatography. Des-38-62-proinsulin, in which all but six amino acids of C-peptide were deleted was not processed by either enzyme. The mutant Lys64,Arg65 to Thr64,Arg65 was not cleaved by the type II enzyme but was still a substrate for the type I enzyme. The mutant Arg31,Arg32 to Arg31,Gly32 correspondingly was not cleaved by the type I enzyme; however, in this case it was not attacked by the type II enzyme. These results indicate that not only is the presence of a dibasic sequence essential, but also that the secondary structure of the protein is important in determining whether the prohormone is susceptible to proteolytic processing.

Animals↗
PubMed1989

A major C-peptide deletion prevents secretion of a mutant human proinsulin from transfected monkey kidney cells.

The biosynthesis and secretion of human proinsulin and a mutant human proinsulin with a major deletion in the C-peptide, (des 38-62)proinsulin, was studied in monkey kidney cells (Cos-7) transfected with cDNAs encoding the respective normal or mutant human preproinsulins. Transfected cells were labelled with [3H]leucine, and insulin-like material was immunoprecipitated and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. It was found that the prepeptide was removed from both the normal and mutant preproinsulins, and that there was no further processing to insulin. The normal proinsulin was rapidly released from the transfected cells, with little intracellular accumulation, while the mutant proinsulin was retained within the cell, with only small quantities of radio-labelled material in the medium. The intracellular mutant proinsulin was membrane bound and located predominantly within a microsomal fraction. These results suggest that C-peptide plays an important role in the efficient transfer of proinsulin through the early stages of the secretory pathway.

Amino Acid Sequence↗
PubMed1989

Lung centroid pressure in immersed man.

Upright immersion imposes a pressure imbalance between alveolar and mean external thoracic pressure. Lung centroid pressure (PLC) is defined as the breathing pressure required to remove this imbalance. Static transrespiratory pressure-volume relationships were determined in subjects immersed in upright (n = 17) and prone (n = 13) postures. Compliances measured during immersion (1.87 +/- 0.15 liter.kPa-1 upright, 1.87 +/- 0.17 liter.kPa-1) prone) were compared with compliances, obtained over the same volume range, while upright in air (1.84 +/- 0.17 liter.kPa-1). PLC was determined by the horizontal (pressure) displacement of immersed compliance curves. PLC was calculated to be +1.33 +/- 0.11 kPa (+13.6 cmH2O) relative to the sternal notch when upright and -0.69 +/- 0.12 kPa (-7.0 cmH2O) relative to the sternal plane when prone (mean +/- SEM). Upright PLC did not support the widely used value of +19 cmH2O (Jarrett AS. J Appl Physiol 1965;20:1261-1266). Analysis shows that when data from earlier investigations were adjusted for differences in reference pressure, the collective PLC supports the present results.

Adult↗
PubMedDate not supplied

Exercise-induced skeletal muscle growth. Hypertrophy or hyperplasia?

Postnatal skeletal muscle growth in humans is generally ascribed to enlargement of existing muscle fibres rather than to cellular proliferation. Some evidence of muscle fibre division or splitting was provided in the nineteenth century. This evidence has more recently been supported by fibres obtained from regenerating muscle, and from muscle which has undergone stress-induced growth. Numerous investigators have reported indirect evidence for exercise-induced hypertrophy and hyperplasia. These findings are largely founded on secondary observations of fibre size or number differences expressed relative to muscle cross-sectional area. Since these observations in humans are open to methodological criticism, researchers have developed 3 animal models to represent exercise-induced human muscle growth. These include compensatory hypertrophy, stretch-induced hypertrophy, and weight lifting in trained animals. The results and criticisms of the experiments which have used these models are discussed in this review. In studies of muscle cross-sectional area, errors are created by fibres terminating intrafascicularly. Longitudinal growth of such fibres result in an overestimation of fibre number, and with the use of penniform muscles where fibres do not run parallel to the longitudinal axis of the muscle, the error is compounded. It was concluded that hyperplasia is not yet substantiated, and that new fibres, if present, may be the result of the development of satellite cells. Further experiments are required before a definitive answer can be provided. It is suggested that rigidly controlled exercise studies using contralateral control, fusiform muscles with analysis of individually teased muscle fibres be performed.

Animals↗