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Biomedical subjects

D A Smith

Publications and source records attributed to D A Smith.

At least 325 records · Page 18Linked to original sources
PubMed1984

Phosphono dipeptides and piperazine derivatives as antagonists of amino acid-induced and synaptic excitation in mammalian and amphibian spinal cord.

Two novel dipeptides, beta-D-aspartylaminomethylphosphonate (Asp-AMP) and gamma-D-glutamylaminomethylphosphonate (Glu-AMP) are potent and selective N-methyl-D-aspartate receptor antagonists and specifically depress polysynaptic excitation in the cat, rat and frog spinal cords. In the same tissues, 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylic acid (pCB-PzDA) and some related piperazines, are broader spectrum excitatory amino acid antagonists, showing increased potency as kainate and quisqualate antagonists compared with previously described antagonists of this type. These piperazines are more effective as depressants of monosynaptic than of polysynaptic excitation.

Amino Acids↗
PubMed1984

Physical fitness of New Zealand army personnel; correlation between field tests and direct laboratory assessments--anaerobic threshold and maximum O2 uptake.

Performance in two field tests was compared with maximum oxygen uptake (V02max) and anaerobic threshold in 42 male army staff. V02max was measured directly during incremental treadmill exercise. Anaerobic threshold was determined simultaneously from changes in ventilation and gas-exchange. The time to run 2.4 km and the distance covered in 12 minutes were each measured within a week of the laboratory assessments. V02max ranged from 39.8 to 66.0 ml kg-1min-1 with a mean of 50.8 ml kg-1 min-1 (SD 6.2) for the group. Mean anaerobic threshold was 30.7 ml kg-1min-1 (SD 5.5). These values compare favourably with those for other military populations. The time to run 2.4 km averaged 616 s (SD 60) for the group while the mean distance covered in 12 minutes was 2.78 km (SD 0.25). The time for the 2.4 km run showed a significant inverse correlation with both V02max (r = 0.83) and anaerobic threshold (r = 0.81). The linear correlations between 12 min run distance and V02max (r = 0.72) or anaerobic threshold (r = 0.70) were lower. V02max and anaerobic threshold may be justifiably estimated using such field tests.

Adult↗
PubMed1984

Gastrointestinal absorption of the strongly acidic drug proxicromil.

Gastrointestinal absorption of the strongly acidic drug proxicromil has been studied with respect to its physical organic chemistry. The lipophilicity of the drug above pH 6 in octanol-buffer partition experiments is dependent on ion pair formation. Similar trends were demonstrated for the in vitro partition of the compound into GI tissue. The absorption of the compound from the perfused GI tract of rats in vivo was not consistent with classical un-ionized drug absorption theories and indicated the operation of other processes, especially ion pair formation, as major mechanisms of proxicromil absorption.

Animals↗
PubMed1984

The role of convection in the standard fluid-mechanical model for morphogenesis.

The effect of convection on reaction-diffusion instabilities in a visco-elastic medium is studied by using the standard continuum theory of a fluid mixture. The medium is assumed to be in local mechanical equilibrium, and convection is generated by pressure forces which arise if the equilibrium density of the medium changes with its composition. A linear stability analysis shows that reaction-diffusion instabilities proceeding from homogeneous steady states at rest are unmodified by induced convection to first order in concentration changes. We suggest that a non-linear analysis would show convection produces no new instabilities, as a linear analysis of inhomogeneous non-convecting stationary states shows that reaction-diffusion growth rates are reduced by convection at long wavelengths and are otherwise unchanged. For applications in embryology, numerical estimates suggest that convection can be ignored in reaction-diffusion mechanisms for pattern formation, and this conclusion is supported by a dimensional analysis.

Animals↗
PubMed1984

The behavioural effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats.

The selective N-methylaspartate (NMA) receptor antagonist 2-amino-5-phosphonopentanoate (AP5) has been applied to the lumbar region of the spinal cord in conscious rats through chronically implanted intrathecal cannulae. Administration of AP5 was compared with administration of 2-amino-4-phosphonobutyrate (AP4), morphine and control injections. Intrathecal injection of AP5 (250 nmol) produced extensor paralysis in the hindquarters and depression of aversive responses to tail heat (54 degrees C), paw heat (hotplate 56.5 degrees C) and paw pressure. Depression of AP5 of the vocal response to aversive electrical stimuli, applied to the tail, suggested that AP5 produced analgesia independently of locomotor paralysis. Intrathecal injection of morphine (20-30 nmol) produced no observed locomotor effects, but depressed responses to all the aversive stimuli. Intrathecal injection of AP4 had no significant effects. When tritiated AP5 was administered intrathecally, the proportion of radioactivity recovered from the lumbar spinal cord suggested that the concentration of AP5, which produced locomotor depression and analgesia, was likely to have been in the range (15-75 microM) known to depress excitatory transmission in isolated spinal cord preparations. It is concluded that synaptic activation of n-methylaspartate receptors is important in spinal pathways which control locomotion, posture and central transmission of nociceptive information.

2-Amino-5-phosphonovalerate↗
PubMed1984

Structure-activity relations of dipeptide antagonists of excitatory amino acids.

Structure-activity relations of dipeptides related to gamma-D-glutamylglycine have been investigated with respect to the ability of these substances to antagonize depolarizing responses of frog motoneurones in vitro to N-methyl-D-aspartate, kainate and quisqualate. A terminal phosphono group was optimal for N-methyl-D-aspartate antagonist activity in relation to both potency and selectivity. Substances containing a terminal phosphono group were relatively poor antagonists of kainate or quisqualate responses. Terminal carboxylic and sulphonic groups were both effective with respect to kainate and/or quisqualate antagonism. Sulphonic compounds were the more selective in this type of action because of their low affinity for N-methyl-D-aspartate receptors. Optimum chain length for N-methyl-D-aspartate antagonism was between one and two carbon atoms shorter than for optimum kainate/quisqualate antagonist activity. Bulky groups within the N-acylated amino acid moiety generally, but differentially, reduced the ability of the substance to antagonize responses to each of the three agonists. Glutamyl peptides were generally more effective than aspartyl peptides of the same overall chain length. However, the most potent dipeptide (selective for N-methyl-D-aspartate antagonism) was the aspartyl derivative, beta-D-aspartylaminomethyl phosphonate, for which there was no glutamyl equivalent. Other useful substances to emerge from this study include the relatively selective kainate/quisqualate antagonists, gamma-D-glutamylaminomethyl sulphonate and gamma-D-glutamyltaurine. If similar selectivity is shown in other preparations also, these substances may prove preferable to gamma-D-glutamylglycine as antagonists of synaptic excitation mediated by kainate or quisqualate receptors.

Amino Acids↗
PubMed1984

Universal cutaneous depigmentation following phenytoin-induced toxic epidermal necrolysis.

A 10-year-old black girl with a severe hypersensitivity reaction to phenytoin is described. Adverse effects included interstitial nephritis, hepatitis, and toxic epidermal necrolysis. An apparently permanent sequela of universal cutaneous depigmentation developed. Although the presence of clear cells in the basal layer of the epidermis suggested that melanocytes might still be present, these clear cells were shown, by electron microscopy, to be Langerhans cells and not melanocytes. This patient demonstrates a unique outcome, not previously described in the literature.

Chemical and Drug Induced Liver Injury↗
PubMed1984

The time course during 36 weeks' endurance training of changes in Vo2 max. and anaerobic threshold as determined with a new computerized method.

Six healthy male subjects followed a programme of endurance training for 36 weeks. At 12 week intervals each underwent an incremental exercise test to maximum on a treadmill. Minute ventilation, cardiac frequency, expired and endtidal concentrations of oxygen and carbon dioxide, oxygen uptake and carbon dioxide output were measured continuously during each test. Anaerobic threshold (AT) was determined non-invasively as the onset of sustained increases in each of the ventilatory equivalent for oxygen, expired and end-tidal concentrations of oxygen followed by an increase in ventilatory equivalent for carbon dioxide after a brief delay due to isocapnic buffering. A new computerized cumulative-sum method was employed. Significant increases in maximum oxygen uptake (Vo2 max.) of 13.6%, AT (32.3%) and % AT/Vo2 max. (17.0%) and a significant decrease (10.2%) in cardiac frequency at an oxygen uptake of 1.0 litres/min (fc1.0) were observed at the completion of the training programme. The time courses of the changes for each of AT, Vo2 max. and fc1.0 were not identical during the training. Compared with Vo2 max. the disproportionate increases in AT occurred earlier and were usually completed within 12 weeks. Vo2 max. increased for the first 24 weeks of training, but showed no further increase over the final 12 weeks fc1.0 decreased through the whole training period. The improved AT after training is more likely to be related to improved peripheral utilization of oxygen than to an improved oxygen delivery to muscles.

Adult↗
PubMed1984

The isolation of lambda phage carrying DNA from the histidine and isoleucine-valine regions of the Bacillus subtilis chromosome.

From a lambda gtWES library of the chromosome of Bacillus subtilis, phages carrying DNA from the hisA and ilv-leu regions were isolated. They were identified by their ability to form complementing plaques on hisB, ilvC or leuB mutants of Escherichia coli K12 under selective conditions and in the presence of a helper phage. The his phages complemented E. coli his A, B or D mutations and could transform seven mutations in the hisA region of the B. subtilis chromosome; each carried a single EcoR1 insert of about 8.2 kb. Phages complementing E. coli ilvC or leuB mutations and carrying the equivalent B. subtilis genes ilvC and leuC transformed a range of mutations in the B. subtilis ilv-leu region. The distribution of genetic markers carried by the phages suggests that the entire ilv-leu cluster from az1A through leuD is covered in the collection of phages obtained and is carried in three EcoR1 restriction fragments of approximately 6.7, 4.7 and 2.85 kb.

Bacillus subtilis↗
PubMed1984

Sacral fractures.

The sacral spine has received relatively little attention in the orthopedic and neurosurgical literature, in part because of the infrequency of developmental, degenerative, or neoplastic conditions of the sacrum requiring surgical intervention. This neglect is unwarranted in trauma, however, because sacral fracture and its associated neural deficit are both common and often complex problems. The sacrum and pelvis behave as a single functional unit; an understanding of the principles of sacropelvic stability has obvious relevance in planning the occasional resection of a sacral tumor and in dealing with the common problem of massive pelvic trauma. A classification of sacral fractures is reviewed along with the usual patterns of neurological involvement. Through analysis of an institutional series of cases, a specific attempt is made to correlate varying types of vertical sacral fractures with differing types of pelvic injury. The radiographic and physiological investigation of sacral fractures is reviewed, as are the various options for achieving the reduction, decompression, and stabilization of sacral fractures.

Biomechanical Phenomena↗
PubMed1984

Pharmacokinetics and toxicity testing.

The pharmacokinetic basis for the design of toxicity tests is discussed with reference to the absorption and clearance of drugs. The absorption and clearance of a wide range of drugs by laboratory animals and man has been examined and reviewed to provide a firm basis against which new drugs can be compared. Some pitfalls in either the empirical approach to toxicology or the incorrect interpretation of kinetic data are highlighted. An approach is outlined for the rational application of animal pharmacokinetic data in the assessment of the safety in man of a new therapeutic agent.

Administration, Oral↗
PubMed1984

Hyperlinear palms in atopic dermatitis: a manifestation of ichthyosis vulgaris?

It has recently been suggested that hyperlinear palms seen in atopic dermatitis are actually a manifestation of concomitant ichthyosis vulgaris. Patients with atopic dermatitis were examined in our clinic for the presence or absence of ichthyosis vulgaris and/or hyperlinear palms. While 70 percent of the patients with atopic dermatitis and ichthyosis did have hyperlinear palms, only 29 percent of the patients with atopic dermatitis and hyperlinear palms had concomitant ichthyosis vulgaris. These findings do not support the suggestion that hyperlinear palms in atopic dermatitis are a manifestation of concomitant ichthyosis vulgaris.

Adolescent↗