Showing papers by "University of Hertfordshire published in 1994"

Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11.

Abstract: OBJECTIVE: To investigate the social adjustment in childhood of people who as adults have psychiatric disorders. DESIGN: Subjects in a prospectively followed up cohort (the national child development study) who had been admitted as adults to psychiatric hospitals were compared with the rest of the cohort on ratings of social behaviour made by teachers at the ages of 7 and 11 years. SUBJECTS: 40 adult patients with schizophrenic illnesses, 35 with affective psychoses, and 79 with neurotic illness who had been admitted for psychiatric reasons by the age of 28. 1914 randomly selected members of the cohort who had never been admitted for psychiatric treatment. MAIN OUTCOME MEASURES: Overall scores and scores for overreaction (externalising behaviour) and underreaction (internalising behaviour) with the Bristol social adjustment guide at ages 7 and 11. RESULTS: At the age of 7 children who developed schizophrenia were rated by their teachers as manifesting more social maladjustment than controls (overall score 4.3 (SD 2.4) v 3.1 (2.0); P < 0.01). This was more apparent in the boys (5 (2.6)) than the girls (3.4 (1.8)) and related to overreactive rather than underreactive behaviour. At both ages prepsychotic (affective) children differed little from normal controls. By the age of 11 preneurotic children, particularly the girls, had an increased rating of maladjustment (including overreactions and underreactions). CONCLUSION: Abnormalities of social adjustment are detectable in childhood in some people who develop psychotic illness. Sex and the rate of development of different components of the capacity for social interaction are important determinants of the risk of psychosis and other psychiatric disorders in adulthood.

The analysis of pharmaceutical compounds using electrochromatography

Abstract: Electrochromatography couples the very high efficiencies associated with capillary zone electrophoresis, with reversed-phase liquid chromatography (RPLC). Therefore, electrochromatography couples the differences in electrophoretic mobilities of related species, with the modification of selectivities that are available to users of RPLC through variation of the stationary and mobile phases. Electrochromatography uses an electric field to drive the mobile phase through a packed capillary, and because the resulting flow profile is plug-like, very high efficiencies are achieved. Also, the linear flow through a packed capillary in electrochromatography is independent of the particle diameter, and since the driving force (electroosmosis) produces no hydrostatic pressure, it is possible to use very small diameter particles and consequently generate large theoretical plate values often>300,000 plates per metre with reduced plate heights<1. The capabilities of electrochromatography are demontrated by means of the analysis of several drug compounds.

Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.

Abstract: In rheumatoid and osteoarthritis, degradation of articular cartilage is mediated by the matrix metalloproteinases collagenase, stromelysin and gelatinase. The key event in this process is the cleavage of triple helical collagen by collagenase. We have determined the crystal structure of the catalytic domain of human recombinant fibroblast collagenase complexed with a synthetic inhibitor at 2.2 A resolution. The protein fold is similar to the amino termini of the zinc endopeptidases astacin thermolysin and elastase despite a lack of primary sequence homology. The conformation of the bound inhibitor provides a molecular basis for the design of inhibitors of collagenase and other matrix metalloproteinases. Such inhibitors should be useful in the treatment of a variety of diseases including arthritis and cancer.

Bi-stable memory element

Abstract: A bi-stable memory element (1) comprises a base contact (3), and a bridging contact (8), both made from an electrically conductive material. The bridging contact (8) is dimensioned so as to have two stable positions, in one of which the bridging contact (8) is in contact with the base contact (3), and in the other of which the bridging contact (8) is spaced apart from the base contact (3). Deflection means (4, 5) deflects the bridging contact (8) from one stable position to the other.

The illusion of control and optimism about health : on being less at risk but no more in control than others

Abstract: If unrealistic optimism is simply a manifestation of the illusion of control (McKenna, 1993), differences in estimates of the likelihood of events for the self and others (comparative optimism) should have concomitant differences in perceived capacity to control these events. This possibility was tested in the domain of health, along with Perloff & Fetzer's (1986) risk-factor version of this downward comparison hypothesis and the hitherto neglected possibility that unrealistic optimism is an artifact of the comparative procedures employed in studies to date. It was found that likelihood judgements for a range of illnesses tended to be significantly lower when made by subjects providing self-ratings than when made by those providing judgements for the 'typical' student and, to a lesser extent, those making judgements for a friend's friend, but not by those doing so for an acquaintance. This comparative optimism was associated with equivalent differences in perceptions of these targets on a selection of relevant risk factors, but not in ratings of their capacity to control these outcomes (for which there was consensus across targets). The data are thus consistent with the risk-factor version of the hypothesis rather than the control version or the artifact explanation. The theoretical implications of these findings are addressed along with their consequences for health promotion.

The nematophagous fungus Verticillium chlamydosporium produces a chymoelastase-like protease which hydrolyses host nematode proteins in situ.

Abstract: The nematophagous fungus Verticillium chlamydosporium secreted several proteases in submerged culture in which soya peptone was the sole carbon and nitrogen source. One protease, VCP1 (M r 33000, pl 10.2), was purified 14-fold from culture filtrates to apparent homogeneity using preparative isoelectric focusing in free solution, and shown to rapidly hydrolyse the chymotrypsin substrate Suc-(Ala)2-Pro-Phe-pNA and elastin. VCP1 had a K m for Suc-(Ala)2-Pro-Phe-pNA of 4.3 × 10-5 M and a k cat of 5.8 s-1. It was highly sensitive to PMSF and TPCK, but only moderately sensitive to chicken egg-white and soya bean trypsin inhibitors. VCP1 degraded a wide range of polymeric substrates, including Azocoll, hide protein, elastin, casein and albumin, and accounted for most of the non-specific protease activity detected in culture filtrates. The purified enzyme hydrolysed proteins in situ from the outer layer of the egg shell of the host nematode Meloidogyne incognita and exposed its chitin layer. VCP1 was secreted by several isolates of V. chlamydosporium and V. lecanii, pathogens of nematodes and insects respectively, but not plant-pathogenic species of Verticillium. These observations suggest that VCP1 or similar enzyme(s) may play a role in the infection of invertebrates.

Reverse accumulation and attractive fixed points

Abstract: We apply reverse accumulation to obtain automatic gradients and error estimates of functions which include in their computation a convergent iteration of the form y= Φ(y,u), where y and u are vectors. We suggest an implementation approach which allows this to be done by a fairly routine extension of existing reverse accumulation code. We show how to re-use the computational graph for the fixed point constructor Φ so as to set explicit stopping criteria for the iterations, based on the gradient accuracy required. Our construction allows the gradient vector to be obtained to the same order of accuracy as the objective function values (which is in general the best we can hope to achieve), and the same order of computational cost (which does not explicitly depend upon the number of independent variables.) The technique can be applied to functions which contain several iterative constructions, either serially or nested

GR113808: a novel, selective antagonist with high affinity at the 5‐HT4 receptor

Abstract: 1. The 5-HT4 receptor has only recently been identified but has yet to be cloned. This paper describes the pharmacology of a potent and selective 5-HT4 receptor antagonist, GR113808, which will be useful in the further characterization of this receptor. 2. On the guinea-pig ascending colon, GR113808 (1 nM-0.1 microM) behaved as an antagonist of 5-hydroxytryptamine (5-HT)-induced contraction, producing rightward displacements of the concentration-effect curve to 5-HT and a concentration-related depression of the maximum effect. However, the compound had no effect on cholecystokinin (CCK-8)-induced contraction in concentrations up to 1 microM. 3. In the guinea-pig colon preparation, onset and offset of the antagonism by GR113808 of 5-HT-induced contraction was examined. Incubation of the tissues for either 15 min, 30 min or 60 min produced similar rightward displacements of the concentration-effect curves to 5-HT, with no increase in the degree of depression of the maxima with increasing time of incubation. Experiments examining offset of antagonism (0.01 microM) demonstrated that washout for 30 min was required to reverse fully the effects of the antagonist. 4. Potency estimates in the colon for GR113808 were made by determining approximate pA2 values (30 min) using the Gaddum equation. The values obtained were 9.2, 9.7 and 9.2 when tested against the agonists 5-HT, 5-methoxytryptamine and R,S-zacopride respectively. 5. On the carbachol-contracted tunica muscularis mucosae preparation of the rat thoracic oesophagus, GR113808 behaved as an antagonist of 5-HT-induced relaxation, producing no reduction in maximum response.(ABSTRACT TRUNCATED AT 250 WORDS)

Interacting effects of CO2 concentration, temperature and nitrogen supply on the photosynthesis and composition of winter wheat leaves

Abstract: Winter wheat (Triticum aestivum L., cv. Mercia) was grown at two different atmospheric CO, concentrations (350 and 700 mu mol mol(-1)) two temperatures [ambient temperature (i.e. tracking the open air) and ambient +4 degrees C] and two rates of nitrogen supply (equivalent to 489 kg ha(-1) and 87 kg ha(-1)). Leaves grown at 700 mu mol mol(-1) CO2 had slightly greater photosynthetic capacity (10% mean increase over the experiment) than those grown at ambient CO2 concentration, but there were no differences in carboxylation efficiency or apparent quantum yield. The amounts of chlorophyll, soluble protein and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) per unit leaf area did not change with long-term exposure to elevated CO2 concentration. Thus winter wheat, grown under simulated field conditions, for which total biomass was large compared to normal field production, did not experience loss of components of the photosynthetic system or loss of photosynthetic competence with elevated CO2 concentration. However, nitrogen supply and temperature had large effects on photosynthetic characteristics but did not interact with elevated CO2 concentration. Nitrogen deficiency resulted in decreases in the contents of protein, including Rubisco, and chlorophyll, and decreased photosynthetic capacity and carboxylation efficiency. An increase in temperature also reduced these components and shortened the effective life of the leaves, reducing the duration of high photosynthetic capacity.

Pathogenicity of the entomogenous fungi Metarhizium anisopliae and Beauveria bassiana against crucifer pests and the honey bee

Abstract: The susceptibility of the cabbage stem flea beetle (Psylliodes chrysocephala; Coleoptera: Chrysomelidae) to different isolates of the entomogenous, hyphomycete fungi Beauveria bassiana and Metarhizium anisopliae, all from heterologous hosts, was investigated. The most pathogenic isolates were of M. anisopliae (V208, V233, V234, V242, V245, and V248). Studies were conducted to determine the virulence of V208 and V245, and their specificity for three other crucifer pests, Phaedon cochleariae, Myzus persicae and Lipaphis erysimi and a beneficial insect, Apis mellifera. Flea beetle mortality rates increased with dose; the estimated LC50 S of V208 and V245 at 14 days post‐inoculation were c. 106 conidia ml‐1. The respective estimated LT50 values of V208 and V245 for P. chrysocephala at 1 × 107 conidia ml‐1 were 10.0 and 9.3 days, and at 1 × 1010 conidia ml LT50s were 3.8 and 4.2 days. Both V208 and V245 were pathogenic for P. cochleariaeM. persicae and L. erysimi. Myzus persicae and L. erysimi died within 4 da...

The relationship between red edge and chlorophyll concentration in the Broadbalk winter wheat experiment at Rothamsted

Abstract: The concentration of chlorophyll in a crop can be related to both the position of the red edge in a reflectance spectrum and the yield of that crop. The use of a remotely-sensed red edge to estimate yield is dependent upon a well-understood relationship between chlorophyll concentration and yield and a poorly understood relationship between red edge and chlorophyll concentration. To determine the form of the relationship between red edge and chlorophyll concentration a field experiment was undertaken using a wheat crop with an exceptionally large range of chlorophyll concentrations. The non-linear form of the relationship between red edge and chlorophyll concentration meant that estimates of red edge could be used to estimate chlorophyll concentration up to 0·5mgg−1 and thereby yield up to 6t −1.

Screen‐printed voltammetric and amperometric electrochemical sensors for decentralized testing

Abstract: This review describes the design and fabrication of screen-printed voltommetric and amperometric electrochemical sensors, together with their applications for decentralized monitoring of several naturally occurring biomolecules, drugs, and potential environmental and industrial pollutants or toxins.

Recommendations for the performance of UDS tests in vitro and in vivo.

Abstract: The Working Group (WG) dealt with the harmonization of routine methodologies of tests for unscheduled DNA synthesis (UDS) both in vitro and in vivo. In contrast to the existing guidelines from OECD, EPA and EC on in vitro UDS tests (there is no Japanese UDS guideline), the Working Group recommends that in general in vitro UDS tests should be performed with primary hepatocytes. For routine applications any other cell types would need special justification. Hepatocytes from male rats are preferable, unless there are contra-indications on the basis of e.g. toxicokinetic data. According to the OECD, EPA and EC guidelines, UDS may be analysed by means of autoradiography (AR) or liquid scintillation counting (LSC). The WG recommends use of AR. LSC is less suitable due to the problem of differentiation between UDS activity and replicative DNA synthesis, and the disadvantage that cells cannot be analysed individually. Since a specific cell type was recommended by the WG, methodological aspects could be described in more detail than in the present guidelines. For in vitro tests, it was agreed that the initial viability of freshly isolated hepatocytes should be at least 70%. With regard to the need for confirmatory experiments in the event of a clear-cut negative result, the majority view was that confirmation by a second (normally not identical) experiment is still needed; this is in line with the present OECD and EC guidelines. Evaluation of results from UDS tests should be based primarily on net nuclear grain (NNG) values, although it is recognised that nuclear and cytoplasmic grains result from different biological processes. Since grain counts are influenced by a number of methodological parameters, no global threshold NNG value can be recommended for discrimination of positive and negative UDS results. For in vitro assays, the criteria for positive findings go beyond those of the present guidelines and two alternative approaches are given which are based on (1) dose-dependent increases in NNG values and (2) reproducibility, dose-effect relationship and cytotoxicity. At present there is no official guideline on the performance of in vivo UDS tests. Some fundamental recommendations given for in vitro methodology also apply to the in vivo assay. For routine testing with the in vivo UDS test, again the general use of hepatocytes from male rats is recommended. However, concerning the requirement to use one or two sexes, consistency with other in vivo genotoxicity assays (e.g. the micronucleus assay) would be preferable. As for the in vitro methodology, AR is preferred rather than LSC.(ABSTRACT TRUNCATED AT 400 WORDS)

Membrane potential‐dependent calcium transport in right‐side‐out plasma membrane vesicles from Zea mays L. roots

Abstract: Right-side-out plasma membrane Vesicles isolated from Zea mays roots were used to study membrane potential (Delta Psi)-dependent Ca2+ transport. Membrane potentials were imposed on the vesicles using either K+ concentration gradients and valinomycin or SCN- concentration gradients, and the size of the imposed Delta Psi was measured with [C-14]tetraphenylphosphonium. Uptake of Ca-45(2+) into the vesicles was stimulated by inside-negative Delta Psi. The rate of transport increased to a maximum at a Delta Psi of about -80 mV and then declined at more negative Delta Psi. When extravesicular Ca2+ concentration was varied, uptake was maximal in the range 100-200 mu M Ca2+. Neither dihydropyridine nor phenylalkylamine Ca2+ channel blockers had any effect on Ca2+ uptake but 30 mu M ruthenium red was completely inhibitory with half maximal inhibition at 10-15 mu M ruthenium red. Calcium transport was also inhibited by inorganic cations. Zn2+, Gd3+ and Mg2+ inhibited by a maximum of 30% while La3+, Nd3+ and Mn2+ inhibited by 70%. The inhibitory effects of La3+ and Gd3+ were additive. Lanthanum-insensitive Ca2+ tive Ca2+ transport was totally inhibited by 80 mu M Gd3+ and showed maximum activity at a Delta Psi of -80 mV, with less uptake at both higher and lower Delta Psi. Lanthanum and Gd3+ also inhibited Ca2+ uptake into protoplasts isolated from Zea roots and their individual and combined effects were similar in extent to those observed with plasma membrane vesicles. It is concluded that maize root plasma membrane contains two Ca2+-permeable channels that can be distinguished by their susceptibility to inhibition by La3+ and Gd3+. Both are inhibited by ruthenium red but not by other organic Ca2+ channel blockers.

Should relatives be allowed to watch resuscitation

Abstract: The sudden death of someone after an accident at a public event can be difficult for relatives to cope with. Doctors' attention is focused on the patient, and the needs of relatives are often unheard. Sarah Adams describes her feelings when her brother died after falling from his horse at the Windsor international three day event, and a doctor who was on duty at the event gives his view. We asked an anaesthetist who was a member of the Resuscitation Council, a cardiologist who runs a resuscitation training course, and a general practitioner with a special interest in ethics to comment on Sarah Adam's wish to be present during attempts to resuscitate her brother

Differences between three rat strains in sensitivity to prepulse inhibition of an acoustic startle response: influence of apomorphine and phencyclidine pretreatment.

Abstract: In the present study we have examined the effect of varying three prepulse parameters (prepulse intensity, prepulse duration, prepulse-pulse interval) on the level of prepulse inhibition (PPI) in Lister hooded, Wistar and Sprague-Dawley rats. The results indicate that each strain showed subtle differences in sensitivity to the prepulse. For instance, Sprague-Dawley and Lister hooded rats showed PPI to prepulses of lower saliency compared to Wistar rats. Optimal prepulse parameters were selected for each strain to examine the effects of apomorphine and phencyclidine on PPI. Further inter-strain differences were noted; apomorphine (0.1-1 mg/kg) increased startle amplitude in Lister hooded and Sprague-Dawley, but not Wistar rats. PPI was attenuated in each strain by apomorphine pretreatment. In a final series of experiments, phencyclidine disrupted PPI in each strain, although with greater potency in the Lister hooded rats. A marked behavioural syndrome was seen at phencyclidine doses that disrupted PPI. It is concluded that rat strain and prepulse parameters are important variables in studying drug effects on PPI.

A review of the toxicology of salbutamol (albuterol).

Abstract: This paper reviews the published toxicology of salbutamol. Salbutamol is a relatively selective beta 2-adrenoreceptor stimulant with rapid, potent bronchodilator activity and only minor inotropic or chronotropic effects. It was not found to be mutagenic. LD50 values and other acute studies indicated low toxicity. Findings published for repeat dose studies were mainly uneventful. Tachycardia and flushing of the skin were observed in dogs. There were several findings peculiar to the rat--growth of the salivary gland, enlargement of the Harderian gland, an increase in colloid in the pituitary, and mesovarian leiomyomas. Increases in heart weights associated with inflammation, hypertrophy of muscle fibres, focal myocardial necrosis and fibrosis were seen in rats. Malformation, in the form of cleft palate, was reported in mice but not in rats or rabbits. These treatment related effects reported for salbutamol are not compound-related but rather are class-related. They are an expression of pharmacological activity brought about by the excessive beta stimulant action of high dosage with the drug.

Ray tracing method and apparatus for projecting rays through an object represented by a set of infinite surfaces

Abstract: Each object in a 3-dimensional image to be displayed may be represented by a set of infinite surfaces. Each elementary area of a screen on which the image is to be displayed has a ray projected through it onto the 3-dimensional image. The location of the intersection of the projected ray with each surface is then determined and from these locations it is determined whether any intersected surface is visible at that elementary area. The elementary area is then shaded for display in dependence on the result of the determination.

The cross-sectional areas of normal equine digital flexor tendons determined ultrasonographically

Abstract: Summary Fifty-two animals, comprising 22 Irish Draught crosses (Group A), 15 Thoroughbreds (Group B) and 15 ponies (Group C) were examined ultrasonographically using a 7.5 mHz linear array probe and stand-off pad. All animals were free of tendon disease as determined from clinical and ultrasonographical examination. The superficial (SDFT) and deep (DDFT) digital flexor tendons were scanned at 7 transverse (axial) levels between the carpus and metacarpophalangeal joint. Each transverse image was digitised using a commercially available frame grabber and the cross-sectional areas of each tendon at each level measured using a dedicated software application. Excellent accuracy (averaging less than 5%) was demonstrated between the ultrasound generated areas and those measured from the tendons post mortem in 12 limbs. The mean, s.d. and tolerance intervals of both SDFT and DDFT cross-sectional areas at each level were determined for each group of horses. There was no statistically significant difference between Groups A and B and these 2 groups were, therefore, combined for further analysis. The cross-sectional areas of both tendons were statistically smaller for Group C when compared to Groups A and B. The ratio of SDFT to DDFT cross-sectional areas was calculated for each level and this demonstrated less variation between groups. The difference in measurements between limbs of the same horse was analysed. The mean differences for all groups were 9.13 mm2 for the SDFT and 11.64 mm2 for the DDFT. Upper limits (95% of the population) were 22.67 mm2 (SDFT) and 29.22 mm2 (DDFT). Weight (Groups A and C), height and mid-metacarpal circumference (all groups) were measured and these physical parameters related to the tendon size at each level for Groups A and B combined and Group C. Tolerance limits and normograms were calculated. No significant regression was found for the horse group over the range of physical parameters measured while regression was shown for the ponies. The cross-sectional areas measured in this study may be useful for determining increased tendon size in cases of bilateral tendonitis or where there is minimal disruption to the internal ultrasonographic architecture of the tendon.