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Biomedical subjects

L Henderson

Publications and source records attributed to L Henderson.

At least 73 records · Page 4Linked to original sources

Visuospatial difficulties and clumsiness: on the interpretation of conjoined deficits.

Sixteen children with motor difficulties and 16 controls, matched on age, gender and verbal I.Q., were assessed on the Test Of Motor Impairment, various graphic tasks and a measure of visuospatial discrimination. Poor perceptual and motor performance tended to co-occur but contrary to the visuospatial deficit account of clumsiness these abilities were uncorrelated even when attention was restricted to the less proficient children. There was no tendency for the control group's superiority in graphic reproduction to diminish when visual feedback was withheld. Some suggestions are offered concerning more appropriate methods for framing and testing causal deficit hypotheses.

Aptitude↗

Distribution of bradykinin B2 receptors in target cells of kinin action. Visualization of the receptor protein in A431 cells, neutrophils and kidney sections.

Peptides corresponding to sequences derived from predicted extra- and intracellular loops of the rat bradykinin receptor were analyzed for interspecies homology as well as for matches within the present dataset of protein sequences to provide a theoretical basis for the specific recognition of the native cognate protein by antibodies raised against these antigens. Application of polyclonal antibodies raised against the selected peptides allowed the immunocytochemical localization of the native receptor protein in cells of rat and human origin. The detection of the molecule was achieved by different immunohisto- and immunocytochemical methods in combination with light, fluorescence, confocal optical laser and electron microscopy. These results were compared to localization studies by autoradiography. Distribution and subcellular localization were determined in human neutrophils, human epithelial carcinoma cells (A431) and in rat kidney tissue.

Amino Acid Sequence↗

Genotoxicity testing of pidotimod in vitro and in vivo.

The mutagenic potential of pidotimod ((R)-3-[(S)-(5-oxo-2- pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was assessed in a series of five assays designed to measure gene mutation, chromosomal damage and primary DNA damage. All tests were carried out in accordance with appropriate EEC and OECD Guidelines. No indications of mutagenic potential were observed in any of the assays.

Animals↗

Induction of micronuclei in rat bone marrow and peripheral blood following acute and subchronic administration of azathioprine.

The frequency of micronuclei was assessed in polychromatic erythrocytes of bone marrow and in polychromatic and normochromatic erythrocytes in peripheral blood of rats following exposure to azathioprine for 28 days. This was compared with the incidence of micronuclei in bone-marrow following exposure to a single dose of azathioprine. The incidence of micronuclei in bone-marrow polychromatic erythrocytes at the maximum tolerated dose (10 mg/kg) following exposure for 28 days was 29.5/1000. The incidence of micronucleated polychromatic erythrocytes in the peripheral blood at this dose was 4.4/1000. At the maximum tolerated dose in the single-dose study (40 mg/kg) the incidence obtained at 48 h post-treatment was 15.7/1000. This supports the view that the use of animals in a subchronic toxicity study is at least as sensitive for assessing in vivo clastogenic activity as an acute study and could reduce animal usage in toxicology assessments.

Animals↗

Effects of maternal ingestion of low-dose aspirin on the fetal cardiovascular system.

OBJECTIVE: Our purpose was to assess fetal central and regional hemodynamics in normal fetuses using two-dimensional, range-gated pulsed Doppler echocardiography in pregnant women on chronic baby aspirin regimen (87 mg). STUDY DESIGN: Fifteen fetuses exposed to maternal chronic ingestion of baby aspirin were compared with 26 control fetuses. Longitudinal studies of the umbilical artery waveform and blood flow through the fetal right and left ventricles were obtained every 4 weeks during gestation in a group of fetuses exposed to daily maternal intake of 87 mg of aspirin. Pulsed Doppler waveforms were obtained below the tricuspid and mitral valves, at the level of the descending aorta (below the ductus), and at the level of the fetal renal artery as it enters the kidney. All tracings were recorded on a strip chart and analyzed with a digital light-pen and graphic overlay system. Peak systolic velocity and minimal diastolic velocity were obtained for the umbilical and fetal renal artery. Peak flow velocity and velocity time integral of the pulsed Doppler waveforms of the atrioventricular valves were calculated. Acceleration time/ejection time ratio was obtained for the descending aorta. RESULTS: No significant differences were found among the two groups in either central or regional circulation. CONCLUSION: Chronic daily maternal ingestion of baby aspirin does not significantly affect the central and regional circulation of the fetus.

Aspirin↗

Simple reaction time and predictive tracking in Parkinson's disease: do they converge on a single, fixed impairment of preparation?

Patients with Parkinson's disease exhibit a number. of abnormalities that seem more marked in circumstances in which stimulus and response are predictable in advance. In this article, we consider the prolonged movement onset latencies exhibited by Parkinsonian subjects in the tracking of predictable targets and in the simple reaction time (RT) task. It has been suggested that the performance impairments on both these tasks stem from a common planning deficit. We argue that the Parkinsonian tendency to refrain from predictive tracking cannot be ascribed to an inability to anticipate due to a planning deficit. The data are better accommodated by our alternative thesis that when Parkinsonians' response initiation lags behind that of normal subjects, this is a result of a strategic adaptation to an impairment of the accuracy of movements guided by an internal representation of the target. Our conclusion, that the primary impairment of predictive tracking is one of inaccurate movement execution rather than delayed response initiation, precludes postulation of the same deficit as a source of the selective prolongation of simple RT sometimes found in Parkinson's disease. Moreover, an analysis of the processing demands of the two tasks shows that the predictability that characterizes each of them is quite different in nature. Hence, the impairments in predictive tracking and simple RT tasks are unlikely to stem from a single mechanism that is defective in Parkinson's disease.

Journal Article↗

Distribution of 1-aminobenzotriazole in male rats after administration of an oral dose.

1. 14C-labelled 1-aminobenzotriazole (ABT), a suicide inactivator of cytochrome P450, was synthesized and administered orally to male rats. The rats were killed at 1, 6, 24, 48 or 72 h after dosing and the concentration of total radioactivity in various tissues and organs measured. 2. The compound appears to be absorbed slowly with 50% of the radioactivity remaining in the stomach at 6 h after dosing and maximum plasma and tissue concentrations were observed at 24 h. 3. Approximately 71% of the dose of 14C was excreted in the urine and 12% in the faeces over 72 h, indicating oral absorption of at least 71%. Tissue-to-plasma ratios of 14C were highest in the liver, adrenals and kidneys, which all contain significant amounts of cytochrome P450; the half-lives of elimination for total 14C in liver, adrenals and kidneys were approximately 24, 16 and 12 h, respectively, while the half-life in plasma was approximately 9 h. 4. ABT was metabolized by N-acetylation, with the acetylated product attaining concentrations equal to ABT in the plasma; two other major metabolites were also excreted in the urine namely, the N-glucuronide of 1-aminobenzotriazole and the N-glucuronide of benzotriazole.

Administration, Oral↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗