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Biomedical subjects

L Henderson

Publications and source records attributed to L Henderson.

At least 19 recordsLinked to original sources
PubMed1992

Effect of dietary fat on the in vitro hepatotoxicity of paracetamol.

In the present study, we have examined the effect of dietary fat on paracetamol-induced liver injury in an in vitro rat liver slice model. Rats were fed, for 7-10 days, diets containing either butter or polyunsaturated vegetable margarine, two fat sources commonly consumed in the human diet. Liver slices were then exposed to paracetamol for 2 hr and further incubated for 4 hr without paracetamol. Cell damage in the slices was quantified at 6 hr by measuring leakage of lactate dehydrogenase, increase in water content and potassium loss. Covalent binding of radioactive paracetamol to liver and the membrane fatty acid composition of the liver were also measured. Liver slices from rats fed butter diets were significantly more sensitive to the toxic effects of paracetamol than those from margarine fed rats. The membrane lipid composition of the livers also reflected the differing fatty acid content of the two diets.

Acetaminophen↗
PubMed1992

The effect of presentation and mode of delivery on neonatal outcome in the second twin.

OBJECTIVE: The purpose of this study was to determine if cesarean delivery of the nonvertex second twin improved neonatal outcome. STUDY DESIGN: We examined the maternal and neonatal records from 457 sets of twins delivered from 1985 to 1990. We compared 1- and 5-minute Apgar scores, umbilical artery and vein blood pH values, duration of neonatal hospitalization, the incidence and length of ventilation, intraventricular hemorrhage, birth trauma, and mortality rate between vertex and nonvertex second twins delivered either vaginally or by cesarean section. RESULTS: The presentation and mode of delivery of the second twin was not associated with a significant difference in any of the outcome variables except for the 1-minute Apgar score, which was lower in the nonvertex group delivered vaginally. CONCLUSION: Our data do not support routine cesarean delivery for twins of any birth weight when the second twin is nonvertex.

Apgar Score↗
PubMed1992

Saccadic eye movements in Parkinson's disease: I. Delayed saccades.

The saccadic eye movements of nine patients with Parkinson's disease were compared to those of nine age-matched controls in two paradigms generating volitional saccades. In both paradigms, subjects had to make delayed saccades to peripheral LED targets: a peripheral target appeared 700 msec before a buzzer sounded, the buzzer being the signal to make a saccade to the target. In the first paradigm ("centre-off"), the fixation target was extinguished simultaneously with buzzer onset. In the second ("centre-remain") it was not extinguished until 1000 msec later. The results showed that for outward saccades in both paradigms, there was no difference between Parkinsonian patients and controls, but saccadic latencies were significantly shorter in the "centre-remain" paradigm. The initial outward saccades were indistinguishable from the normal, reflex saccades of the same subjects. However, saccades returning to the centre (a type of remembered target saccade) were hypometric and showed multistepping. Both effects were more pronounced in patients with Parkinson's disease. The significance of these findings in terms of current hypotheses about the nature of the Parkinsonian saccadic deficit is discussed.

Aged↗
PubMed1992

Saccadic eye movements in Parkinson's disease: II. Remembered saccades--towards a unified hypothesis?

Ten patients with mild to moderate Parkinson's disease were compared with ten age-matched normal controls in a series of saccadic paradigms in order to test various hypotheses relating to the origin of the Parkinsonian saccadic defect. The paradigms comprised a reflex saccade paradigm, a standard remembered saccade paradigm, a remembered saccade paradigm with delayed centre-offset, and a remembered saccade paradigm with a second target flash immediately prior to saccade execution. Finally, subjects executed both reflex and remembered saccades in a standard remembered paradigm (the "two-saccade" paradigm). As has been reported previously, Parkinsonian subjects demonstrated hypometria on all remembered saccade paradigms, particularly the "two-saccade" paradigm. There was, however, no significant difference between the first three remembered saccade paradigms. These studies serve to refute a simple attentional capture hypothesis, and a hypothesis that suggests that the abnormality of remembered saccades is due to concurrent reflex saccade suppression. On the basis of the results, further hypotheses are advanced in an attempt to explain all published work on Parkinsonian saccades.

Aged↗
PubMed1992

Reaction time and movement time in children with a Developmental Coordination Disorder.

The Test of Motor Impairment (TOMI) was used to select 12 children with a Developmental Coordination Disorder (DCD) and 12 age-matched controls. In an aiming task, movement latency, movement duration and its variability were significantly prolonged in the DCD group. In a coincidence timing version of the task, absolute timing error was significantly greater in the DCD group. The most robust chronometric effect for differentiating the two groups seemed to be the duration of movement when the target was small. Multiple regression showed that TOMI was a powerful indicator of movement duration.

Child↗
PubMed1992

The metabolism of acitretin and isoacitretin in the in situ isolated perfused rat liver.

1. The metabolism of acitretin and its 13-cis isomer, isoacitretin, has been investigated in the in situ isolated perfused rat liver in order to differentiate the action of the liver from that of the gut on the metabolism of these isomers. 2. Acitretin undergoes alpha-oxidation, chain shortening O-demethylation, and glucuronidation in the perfused rat liver. 3. Isoacitretin undergoes glucuronidation as the major, almost exclusive, route of metabolism in the perfused rat liver. 4. The difference in the hepatic metabolism of the cis and trans isomers of this retinoid may explain the differences in their pharmacokinetics, and may help in understanding the pharmacokinetics of related retinoids.

Acitretin↗
PubMed1992

Evaluation of the genotoxic spectrum of cisplatin for Candida albicans.

The platinum co-ordination complex cisplatin [cis-diamminedichloroplatinum (II)] is a highly effective anticancer drug whose activity derives from its ability to form adducts crosslinking neighbouring purine bases in DNA. Under in vitro conditions, cisplatin induced cellular inactivation, forward and reverse mutations, reciprocal and nonreciprocal mitotic recombinations and phenotypic switching in the opportunistically pathogenic yeast Candida albicans. Mutant and recombinant yields were higher with post-treatment growth at 25 degrees C rather than 37 degrees C: the reverse was true for cell death or phenotypic switches. These responses comport with prior evidence that, generally, the higher recovery temperature discourages DNA repair processes in C. albicans. Thiosulphate, an agent used therapeutically to reduce nephrotoxic side effects of cisplatin in humans, greatly decreased both the lethality and recombinagenicity of cisplatin for C. albicans. Implications of these observations for possible genetic destabilization of C. albicans populations born naturally by cancer patients undergoing treatments with cisplatin are discussed.

Candida albicans↗
PubMed1991

An immunoaffinity immobilized enzyme assay for neomycin phosphotransferase II in crude cell extracts.

An immunoaffinity immobilized enzyme assay for neomycin phosphotransferase II (NPT II) has been developed. This method combines affinity purification with an enzyme-catalyzed reaction. The assay is mechanically simple and can be semiautomatable since all steps are performed in a microtiter plate. An immunoaffinity step separates NPT II from endogenous kinases, which may produce false positive results, and from endogenous phosphatases and inhibitors, which decrease the apparent NPT activity. This method thus exploits two modes of specificity: antigen-antibody specificity and enzyme catalysis specificity. This gives a high degree of specificity and allows quantitation of 0.1 ppm NPT in crude plant protein extracts. The catalytic ability of the NPT is not significantly hampered by its attachment to the gel, in the Km values for ATP and neomycin and the catalytic number for immobilized NPT are comparable to those for the NPT in solution.

Adenosine Triphosphate↗
PubMed1991

Scales for rating motor impairment in Parkinson's disease: studies of reliability and convergent validity.

Study 1 examined the reliability of the ratings assigned to the performance of five sign-and-symptom items drawn from tests of motor impairment in Parkinson's disease. Patients with Parkinson's disease of varying severity performed gait, rising from chair, and hand function items. Video recordings of these performances were rated by a large sample of experienced and inexperienced neurologists and by psychology undergraduates, using a four point scale. Inter-rater reliability was moderately high, being higher for gait than hand function items. Clinical experience proved to have no systematic effect on ratings or their reliability. The idiosyncrasy of particular performances was a major source of unreliable ratings. Study 2 examined the intercorrelation of several standard rating scales, comprised of sign-and-symptom items as well as activities of daily living. The correlation between scales was high, ranging from 0.70 to 0.83, despite considerable differences in item composition. Inter-item correlations showed that the internal cohesion of the tests was high, especially for the self-care scale. Regression analysis showed that the relationship between the scales could be efficiently captured by a small selection of test items, allowing the construction of a much briefer test.

Activities of Daily Living↗
PubMed1990

Involvement of an NAD(P)H oxidase as a pO2 sensor protein in the rat carotid body.

The rat carotid body tissue reveals a photometrically measurable haem signal with absorbance maxima at 560 nm, 518 nm and 425 nm, suggesting the presence of a b-type cytochrome; this was confirmed by pyridine haemochrome and CO spectra. The quantity of cytochrome b was estimated to be 310 pmol.mg of protein-1. This haem is capable of H2O2 formation, which can be inhibited by 10 microM-diphenyliodonium (DPI). The hypoxia-induced increase in nervous chemoreceptor discharge and the reduction of FAD and NAD(P)+ were also inhibited by DPI (10 microM). These results suggest that an oxidase such as the NAD(P)H oxidase of neutrophils may act as a pO2 sensor protein in the rat carotid body, probably inducing the pO2 chemoreceptor process by H2O2 formation.

Animals↗
PubMed1990

On the peculiarity of simple reaction time.

Two experiments are reported in which high-compatibility reaction time (RT) tasks were performed with, and without, a concurrent secondary task. In both experiments, the secondary task interfered to a greater extent with simple RT than with choice RT. In fact, the effect of adding a secondary task was to eliminate the advantage of simple RT over two-alternative-choice RT. Previous studies of this phenomenon employed a task in which subjects raised a finger when it received tactile stimulation, while engaging in continuous reading aloud. The present experiments show that the effect can be obtained using a different stimulus modality (vision) as well as other responses (vocal) and secondary tasks (shadowing, auditory step-tracking). The paradigm provides a means of isolating preparatory processes that are peculiar to the simple RT task.

Adult↗
PubMed1990

Lonidamine: a non-mutagenic antitumor agent.

Lonidiamine is a novel indazole-carboxylic acid with antitumour properties; it has been studied for potential mutagenicity in a comprehensive battery of tests. In assays for the induction of gene mutations in prokaryotes (Ames test) and eukaryotes (induction of HPRT mutations in CHO cells), negative results were obtained. There was no evidence of the induction of chromosomal damage in cultured mammalian cells in vitro. No mutagenic activity was observed in tests for chromosomal damage in vivo, in somatic cells (micronucleus test) or in germinal cells (dominant lethal test). These negative results are consistent with observations indicating that lonidamine affects cellular energy processes, rather than the mechanisms of cell division. The lack of mutagenic properties suggests that lonidamine may present significant advantages in treatment of some tumours, offering a reduced risk of resistant clones, secondary cancer and heritable genetic damage.

Animals↗
PubMed1990

Antisaccades and remembered saccades in Parkinson's disease.

Antisaccades were studied in ten patients with mild to moderate Parkinson's disease and ten age-matched normal controls. Remembered saccades and reflex saccades were assessed for comparison. In the population of patients who showed the previously reported abnormalities of remembered saccades, antisaccades were indistinguishable from those of controls in latency, gain and peak velocity. This finding implies that antisaccades are mediated through pathways which are unaffected by Parkinson's disease, and which are therefore presumably distinct from pathways mediating other voluntary saccades.

Aged↗
PubMed1990

Induction of mutations in mouse lymphoma L5178Y cells by ethylmethanesulphonate, benzidine and benzo[a]pyrene.

As part of the third UKEMS collaborative trial, the induction of mutations in mouse lymphoma L5178Y cells was analysed by an agar cloning method. The method used was based on the published methods of Clive and co-workers and Amacher and co-workers. Mutations at the thymidine kinase (tk) locus were analysed following exposure to ethylmethanesulphonate (EMS) in the absence of S9 mix, benzo[a]pyrene (B[a]P) in the presence of S9 mix and benzidine (BZD) in the absence and presence of S9 mix. Mutations were induced under all these conditions and no difference was found between a 48-h and 72-h expression period. Small and large colonies on trifluorothymidine (TFT) selective plates were expanded and found to be stably resistant to TFT. The effects of varying the S9 level and the composition of the cofactor mix on the mutagenicity of BZD and B[a]P were also analysed. The ability of BZD to induce mutations at the hprt locus was investigated. No mutations were detected either in the presence or absence of S9 mix.

Animals↗
PubMed1990

DNA alkylations and mutation after exposure to ethyl methanesulphonate in mammalian cell lines routinely used in mutagenicity testing.

DNA ethylations were measured in four mammalian cell lines, Chinese hamster ovary CHO, mouse lymphoma L5178Y t k+/-, human lymphoblastoid TK6 and Chinese hamster V79, following exposure to [3H]ethyl methanesulphonate. Concurrent estimates of cytotoxicity and gene mutation were also carried out. Total DNA-binding and relative levels of ethylation at N-7 guanine (N-7G), O6 guanine (O6G) and N-3 adenine (N-3A) were essentially the same in all four cell lines. Differences in response to EMS between the cell lines, namely the greater cytotoxicity in TK6 cells, would therefore appear to reflect subsequent handling of the DNA lesions, rather than different levels of DNA ethylation in the cell lines.

Adenine↗
PubMed1989

Abnormalities of nonvisually-guided eye movements in Parkinson's disease.

Rapid eye movements (saccades) were examined in 7 patients with idiopathic Parkinson's disease (PD) and a matched group of normal control subjects. The effect of instructional and stimulus conditions used to elicit saccades was examined using 3 experimental paradigms. Eye movements directly elicited by a novel peripheral target were unimpaired in patients with PD as compared with control subjects. Saccades to a remembered target location, however, were dysmetric in the PD group and showed a characteristic multistepping pattern. The PD impairment was not caused by a loss of information on target location since their final eye position was close to the target at all eccentricities. Peak velocity, duration, and latency did not distinguish between PD patients and controls. These results support the view that for saccades which are not directly elicited by a visual target there is a neural pathway that can be distinguished from structures involved in the generation of visually elicited (or 'reflexive') saccades. The finding that in PD saccades to a remembered target are selectively impaired suggests that structures in the basal ganglia play a crucial role in this alternative pathway.

Aged↗