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Biomedical subjects

A Lees

Publications and source records attributed to A Lees.

At least 127 records · Page 7Linked to original sources
PubMed1989

A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra.

The total activity of superoxide dismutase (SOD) and cytosolic and particulate activity of SOD in human substantia nigra and cerebellum were measured by a spectrophotometric method based on the ability of SOD to inhibit the autoxidation of adrenaline. The cytosolic and particulate isoenzymes of SOD were differentiated by the inclusion of potassium cyanide which selectively inhibits cytosolic copper/zinc-dependent SOD activity. In autopsied human brains, there was no difference in total SOD activity, or the activity of SOD in cytosol in substantia nigra of patients dying with Parkinson's disease compared to age-matched controls. However, the activity of the particulate form of SOD was higher in the parkinsonian substantia nigra compared to control tissue. In the cerebellum there was no difference in the total, cytosolic, or particulate activity of SOD between parkinsonian patients and age-matched controls. Increased activity of SOD in particulate fraction may be a protective response to elevated levels of toxic free radicals in the parkinsonian substantia nigra. Alternatively, increased SOD activity may induce cell death through the accumulation of hydrogen peroxide.

Aged↗
PubMed1987

An investigation of the mechanism involved in the cholinergic action of meptazinol.

In concentrations above 20 microM, (+/-)-meptazinol produced a contraction of the guinea-pig isolated ileum and this effect was antagonized by atropine (0.01 to 0.3 microM) in a manner which was not competitive. Cooling the preparation to 15 degrees C blocked the contractile action of meptazinol and of dimethylphenylpiperazinium (DMPP) but did not affect the action of carbachol. Twitch responses of the rat phrenic nerve-diaphragm preparation induced by indirect electrical stimulation in the presence of naloxone (20 nM) were potentiated by meptazinol (1 to 40 microM) which also reversed a partial blockade of the twitch induced by tubocurarine. Neither of these effects was seen in tissues which had been pretreated with the cholinesterase inhibitor BW284C51 (0.2 microM) though tetraethylammonium iodide (40 microM) was still able to enhance the responses to stimulation. In the presence of naloxone (20 nM) electrically induced responses of the rat isolated rectum were abolished by cinchocaine (10 microM), partially blocked by atropine (0.1 to 0.4 microM) and potentiated by meptazinol (1 to 30 microM). The latter action was not seen when meptazinol was administered in the presence of BW284C51. It is concluded that the cholinergic action of meptazinol in these tissues is due to an indirect effect, probably involving inhibition of cholinesterase and that no evidence was seen of any ability to increase the release of acetylcholine itself.

Animals↗
PubMed1986

A bioengineering analysis of human muscle and joint forces in the lower limbs during running.

A two-dimensional, dynamic bioengineering model of the lower limbs was developed in order to estimate muscle and joint forces present during running at 4.5 m s-1. Data were collected from four subjects using a force platform and cine film. Individual X-rays and anthropometric data from the lower limbs were utilized to produce accurate bone models of the subjects' legs. Electromyographic verification of the model was undertaken while a runner was undergoing treadmill running at 4.5 m s-1. Results indicate that peak muscle forces of 22 times subject body weight (22 BW) could be present in the quadriceps muscle group and 7 BW in the gastrocnemius. The anterior shin muscles were found to be active for the first 9% of stance phase only, and compressive loads of 33 BW were found in the knee joint. The relationship between these high forces in the lower limbs and running related injuries is discussed.

Adult↗
PubMed1984

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset.

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p.) for 4 days induced dose-dependent parkinsonism in the common marmoset within 48 h. MPTP produced profound akinesia, rigidity of the trunk and limbs, postural abnormalities, loss of vocalization and, in some cases, postural tremor. In a single animal the administration of L-DOPA in conjunction with a peripheral decarboxylase inhibitor, reversed the parkinsonian symptoms. Subsequent biochemical analysis showed a profound loss of dopamine and [3H]dopamine uptake in the caudate-putamen, but no change in specific [3H]spiperone binding.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1984

Brevin and vitamin D binding protein: comparison of the effects of two serum proteins on actin assembly and disassembly.

Actin depolymerizing activity in serum can be attributed to the two proteins brevin and vitamin D binding protein (DBP). To investigate their mechanisms of action, we used a number of techniques, including procedures involving the fluorescent pyrene-labeled actin probe, to compare the interaction of the two proteins with G- and F-actin in vitro. With a fluorescence enhancement assay, we determined that brevin forms a 1:2 complex and DBP forms a 1:1 complex with pyrene-G-actin. We also found that both proteins reduce the viscosity of F-actin measured with high-shear and low-shear viscometers, with brevin effective at much lower concentrations than DBP. In polymerization experiments, brevin inhibits filament elongation at substoichiometric levels by inhibiting monomer addition at the barbed end but can also accelerate polymerization by nucleating assembly of filaments which grow from the pointed end. DBP does not nucleate filament assembly and inhibits filament elongation at either end only at near-stoichiometric levels. Brevin, but not DBP, accelerates disassembly of filaments diluted into a depolymerizing medium. This is consistent with the capability of brevin to sever preformed filaments associated with erythrocyte membranes and to increase the number of filament ends as estimated by a cytochalasin binding assay. In steady-state experiments involving the use of pyrene-actin, brevin produces only a small increase in the apparent monomer concentration when the critical concentrations at the two ends of the filaments are the same (i.e., in 0.1 M KCl). However, when the critical concentration at the pointed end is higher than that at the barbed end (i.e., in 2 mM MgCl2), low molar ratios of brevin sharply increase the monomer concentration to the critical concentration of the pointed end. This allows substoichiometric amounts of brevin to completely depolymerize filaments when the total actin concentration is at or below that of the pointed end. In contrast to brevin, DBP increases the amount of nonfilamentous actin in a stoichiometric and dose-dependent manner regardless of the nature of the salt in the medium. We conclude from this study that brevin is similar in its mechanism of action to other proteins known to bind to the barbed end of filaments and that DBP is related in its action to proteins that complex monomers and prevent them from participating in the polymerization process.

Actins↗
PubMed1984

Exercise and sports equipment: some ergonomics aspects.

Sports equipment encompasses a gamut of devices used in laboratory, training and competitive contexts and these form the content of this paper. Ergometers range in sophistication from friction braked stationary bicycles to computer controlled simulators which incorporate exercise modes specific to the athletic user. These are now used in training, as experimental devices and in some instances for competition purposes. Training equipment exhibits a similar emphasis on exercise specificity, safety being an important aspect of its use. Design of projectiles for sporting activities has mainly reflected their traditional modes of use, the introduction of synthetic materials having some ergonomics implications. Similarly, materials science and design technology have contributed innovations in equipment for racquet sports and hitting implements. The changes have tended to be associated with availability of new materials for product construction and have implications for safety and skill in the transition to using the new products. Ski equipment design illustrates ergonomics factors in interfacing the performer with the sporting environment and how equipment has progressed by regenerative design processes. Enhancement of performance in some sports must be accompanied by an awareness of safety requirements: where appropriate, risks to participants should be reduced by use of protective clothing and equipment. Enforced validation of protective equipment is recommended to raise safety levels in certain sports and the safety of spectators must not be neglected. Human factors criteria can then be applied in monitoring, officiating and spectating at sporting events.

Journal Article↗
PubMed1982

Brain metastases in breast cancer patients receiving adjuvant chemotherapy.

A retrospective analysis was performed comparing the incidence of brain metastases as a site of first recurrence in patients receiving adjuvant chemotherapy during the period from 1973--1979 for node-positive operable carcinoma of the breast, compared to a matched control group of patients presenting during the same period treated by local measures only. Five of 115 patients (4.3%) receiving adjuvant chemotherapy have had brain metastases as first site of distant recurrence compared to zero of 115 (0%) in the control group. This comprised 12.8% of first distant recurrences in the adjuvant group. The authors suggest that this increased incidence of brain metastases, as site of first recurrence, reflects prolonged suppression of systemic disease by adjuvant chemotherapy with less effect in controlling metastases in the brain.

Adult↗
PubMed1982

Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.

In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time. This compound is the major metabolite of phenylethylamine, the production of which may be disturbed in a number of neuropsychiatric illnesses. Thus plasma measurements might be employed clinically to provide an estimate of central changes in phenylethylamine economy. A small but significantly higher proportion of conjugated phenylacetic acid was present in the plasma (but not cerebrospinal fluid) of Parkinsonians compared with controls.

Female↗
PubMed1979

7-Acetylcytochalasin B: differential effects on sugar transport and cell motility.

Cytochalasin B (CB) is a potent inhibitor of sugar transport and cell motility in animal cells. We have synthesized and characterized the CB derivative 7-acetylcytochalasin B (CBAc) and have found that it has differential effects on transport and motile processes in fibroblasts. The derivative inhibited sugar transport in human red cells, 3T3 cells, and chicken embryo fibroblasts at micromolar concentrations, although it was less potent than its parent compound. Unlike CB, which causes fibroblasts to round up and arborize at less than 10 microM, CBAc had no effect on fibroblast morphology and membrane ruffling at concentrations as high as 90 microM. Competitive binding experiments using [3H] CB showed that the affinity of CBAc for sites related to sugar transport in the red cell membrane is about one-fourth of that of CB. In contrast, similar experiments using [3H] dihydrocytochalasin B (a derivative which inhibits cell motility but not sugar transport) showed that the affinity of CBAc for sites associated with red cell spectrin and actin is only about 1/20 of that of dihydrocytochalasin B. This study demonstrates that acetylation of the C-7 hydroxyl group of CB reduces its effect on cell morphology and motility much more than its ability to inhibit sugar transport. This observation, together with our earlier work with dihydrocytochalasin B, establishes that the pharmacologic effects of CB on fibroblasts result from the binding of the drug to two distinct classes of receptors and that these receptors interact with different parts of the cytochalasin molecule.

Animals↗