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Biomedical subjects

R Butler

Publications and source records attributed to R Butler.

At least 37 records · Page 2Linked to original sources

A 3.5 genome equivalent multi access YAC library: construction, characterisation, screening and storage.

The construction of a yeast artificial chromosome (YAC) primary gridded library of 35,000 clones from human lymphoblastoid (48,XXXX) cell line DNA is described. The average YAC size is approximately 350kb representing a greater than 3.5 times coverage of the genome. The library is stored at -70 degrees C as gridded clones on nylon filters impregnated with 20% glycerol and as glycerol suspensions of individual clones in microtitre plates providing a prolonged multi-user potential. To date we have used 14 single copy probes to screen this library by colony hybridisation as well as PCR and have isolated between 1 and 5 YAC clones for every probe.

Cell Line

Tail docking.

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Animal Welfare

A mycobacterial 65-kD heat shock protein induces antigen-specific suppression of adjuvant arthritis, but is not itself arthritogenic.

A recombinant (r)65-kD protein from Mycobacterium leprae, at levels far in excess of those present in whole mycobacteria, was unable to induce arthritis. Even when combined with a synthetic adjuvant, CP20961, to mimic the peptidoglycan adjuvant component of the mycobacterial cell wall, the r65-kD protein failed to induce arthritis. Pretreatment with as little as 1 microgram r65-kD protein protected rats against arthritis induced by M. tuberculosis, but this r65-kD protein was markedly less able to protect against arthritis induced by the synthetic adjuvant, CP20961, or type II collagen. The r65-kD protein appears, therefore, to produce an antigen-specific protection against arthritis induced by bacterial cell walls containing the 65-kD protein. Such protection can be overcome, however, by arthritogenic T lymphocytes, suggesting that protection occurs by preventing clonal proliferation of autoreactive T lymphocytes that are induced by the adjuvant properties of mycobacterial cell walls. How the r65-kD protein abrogates this particular adjuvant activity, and the nature of the arthritogenic self antigen(s), remain to be elucidated.

Animals

Rapid typing of apolipoprotein B DNA polymorphisms by DNA amplification. Association between Ag epitopes of human apolipoprotein B-100, a signal peptide insertion/deletion polymorphism, and a 3'flanking DNA variable number of tandem repeats polymorphism of the apolipoprotein B gene.

We present here rapid and efficient methods for the analysis of multiple variable apolipoprotein (apo) B loci using polymerase chain reaction based techniques. For illustrative purposes, we have applied these methods to establish an association between these polymorphisms and the apo B Ag immunological epitopes. The 5 DNA polymorphisms include 3 restriction endonuclease sites (for XbaI, EcoRI and MspI), a variable number of tandem repeat (VNTR) locus at the 3' end of the apo B gene, and an insertion/deletion polymorphism involving the signal peptide region of apo B. The latter two newly described polymorphisms are directly detectable following amplification and may have physiological effects on apo B expression because of their critical locations. All of these sites were typed using flanking oligonucleotides and the newly developed polymerase chain reaction. Amplification products were typed either directly (3' VNTR and signal peptide insertion/deletion alleles), or following specific enzyme digestion (for the restriction sites), or by allele specific oligonucleotides. The detailed methods presented will prove generally useful for rapidly typing DNA variation in the apo B gene. Using these techniques, we found a significant linkage disequilibrium between the Ag(t/z) locus and the 3' VNTR, and the Ag(c/g) locus and the signal peptide length polymorphism. Future association studies using these DNA polymorphisms should take into consideration that observed effects may be related to its linkage disequilibrium with the Ag loci and vice versa.

Alleles

The effects of mastery and competitive conditions on self-assessment at different ages.

It was hypothesized that self-evaluative accuracy will increase with age in a competitive condition, while even young children will appraise their performance quite accurately in a mastery condition. Children at ages 5, 7, and 10 working in either a match-the-standard or a competitive condition copied a drawing and then evaluated their copies. As hypothesized, competing 5-year-olds overestimated the quality of their copies, and self-assessments became less positive and better correlated with adult judgments with age. There were no age differences in self-evaluative accuracy in the mastery condition. Examination of children's explanations for their ratings and their interest in the task supported the interpretation that young children are guided by a nonnormative concept of ability, which can lead to overoptimistic perceptions of competence under competition. Older children tended to adopt normative goals and criteria for self-assessment in competition and mastery ones in the match the standard condition, and were realistic about their performance in both.

Aptitude

When pupils do not understand the determinants of their success and failure in school: relations between internal, teacher and unknown perceptions of control and school achievement.

Both dispositional and attributional perspectives on perceptions of control assume that people have some idea of outcome determinants. This, however, may not always be so. This study tested the hypothesis that pupils do not always understand the determinants of their learning outcomes, and that such a sense of unknown control will be associated with poor achievement in school. The study was unusual in that it tapped both dispositional control perceptions, using the new MMPCC, and causal attributions for success and failure in a school examination. Subjects were 186 10-year-old Israeli pupils of heterogeneous SES. Results confirmed that unknown control emerged as a distinct dimension of perceived control in both dispositional and attributional measures, and was consistently associated with poor achievement in school. Attributions of test outcomes to unknown causes were strongly related to dispositional unknown control, and were not affected by success or failure. In contrast, dispositional and attributional internality were unrelated, and did not predict achievement. It is argued that internal beliefs reflect internalised social-educational norms, and as a result have less impact on motivation than perceptions of unknown control. The implications of these findings for educational practice and motivational interventions are discussed.

Achievement

The thieno[3,2-c]pyridine and furo[3,2-c]pyridine rings: new pharmacophores with potential antipsychotic activity.

Two new arylpiperazine derivatives, the 4-(1-piperazinyl)thieno- and -furo[3,2-c]pyridine ring systems, have been synthesized and appended via tetramethylene chains to various imide rings. Target compounds from each series were found to have significant activity in the blockade of apomorphine stereotypy and apomorphine-induced climbing, the Sidman avoidance response, and the conditioned avoidance response. In addition, while potent affinity for serotonin 5-HT1 and 5-HT2 receptors was observed for both the thieno- and furo[3,2-c]pyridine derivatives, the interaction of these molecules with the dopamine D2 receptor was weak. Electrophysiological studies of the lead prototypes from each series, involving compounds 22 and 33, indicate these two molecules have distinctively different effects on dopamine neurons in areas A9 and A10. Despite the similarity these molecules share in their behavioral indices of antipsychotic activity, it is likely that the thieno- and furo[3,2-c]pyridine rings employ different mechanisms to achieve this convergence of biological effects.

Amphetamines

Mastery versus ability appraisal: a developmental study of children's observations of peers' work.

This study was designed to test the hypothesis that there is an age-related shift from mastery enhancement to relative ability assessment in the goal of social comparison. Children at ages 5, 7, and 10 made pictures with stickers under conditions of high or low concern with relative performance (competition/no competition) and high or low procedural ambiguity (free design/copying a drawing). The effects of the manipulations on frequency of glancing at the experimenter and the drawing were similar at all ages; competition enhanced glancing at peers, however, only at ages 7 and 10. The hypothesized shift in the function of social comparison was further supported by age differences in children's explanations for glancing at peers and by the pattern of intercorrelations between glances at the 3 targets and between glances and picture quality. The results indicate how mastery-based comparisons can promote mastery and performance and illustrate some costs older children may pay for their tendency to observe others primarily to assess relative ability.

Achievement

Evidence for a regenerative capacity in adult mammalian cardiac myocytes.

Cardiac muscle does not contain a copopulation of myogenic cells and is mitotically inactive; hence, any regenerative capacity of the myocardium most likely originates from viable fragments of damaged cells rather than mitogenic activity. To assess the extent of such tissue recovery, single doses of the drug bupivacaine were used to induce degeneration of rat ventricular myocytes, and histological evidence for tissue recovery was sought. Up to 1 wk posttreatment, extensive degeneration was found around the injection site. At 2 wk, evidence of regeneration could be seen, and at 3 wk posttreatment, some relatively normal looking tissue was found.

Animals

Interactions of Mycobacterium lepraemurium with resident peritoneal macrophages; phagocytosis and stimulation of the oxidative burst.

Live Mycobacterium lepraemurium or 60Co-gamma-irradiated organisms stimulated a very weak oxidative burst compared with similar numbers of heat-killed organisms or with live M. microti. This was found to reflect the poor uptake of the living organisms rather than an absolute failure to stimulate an oxidative burst. It is possible, however, that phagocytosis of fewer than 3-4 bacteria may not trigger the respiratory burst. Pre-incubating live M. lepraemurium with sera from infected mice, but not with fresh normal mouse sera, resulted in enhanced phagocytosis with a concomitant increase in the oxidative burst. The level of opsonic activity correlated with the M. lepraemurium specific antibody titres. The opsonic activity appeared to be mediated by antigen-antibody activation of the classical complement pathway as heat-inactivation destroyed the activity.

Animals

Macrophage activity in resistant and susceptible mouse strains infected with Mycobacterium lepraemurium.

The level of activation of peritoneal macrophages following subcutaneous inoculation of resistant (C57BL) and susceptible (BALB/c) mice was assessed by monitoring superoxide anion and hydrogen peroxide production and also tumour cell cytostasis. The level of systemic macrophage activation appeared to correlate with bacterial load, rather than resistance to infection. It was observed that the more susceptible (BALB/c) strain developed higher and more sustained levels of systemic macrophage activation, whereas the more resistant (C57BL) strain showed only low transient levels of macrophage activation. In contrast, in vivo challenge of subcutaneously infected C57BL mice, via the intra-peritoneal route, with heat-killed Mycobacterium lepraemurium and thioglycollate resulted in a high level of macrophage activation compared with similarly treated uninfected mice. Similar treatment of susceptible BALB/c mice, however, did not result in enhanced macrophage activation. It was also observed that high levels of macrophage activation occurred in T-cell deprived C57BL mice following infection with M. lepraemurium.

Animals

A monoclonal antibody (BIP 45) detects Ag(c,g) polymorphism of human apolipoprotein B.

A monoclonal antibody (BIP 45) against human apolipoprotein B (apo B) was used to study the polymorphism of apo B in families and in unrelated subjects. BIP 45 bound to apo B-containing lipoprotein particles in one of three distinct patterns of immunoreactivity (strong, weak and intermediate). Family studies showed that these binding patterns result from co-dominant transmission of apo B allelic pairs which are temporarily designated allele BIP- and allele BIP+; allele BIP+ would code for the apo B BIP 45 epitope. Analysis of plasma samples from 244 unrelated men randomly chosen from the North French population indicated that 46.7% of them bound BIP 45 with low affinity (weak reactors), 44.7% with intermediate affinity (intermediate reactors) and 8.6% with high affinity (strong reactors). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.690/0.310 for the type BIP-/BIP+ alleles. This corresponds to the gene frequencies of 0.695/0.305 at the Ag(g)/Ag(c) locus previously found in a Caucasian population. Furthermore, the investigation of Ag(c,g) and of monoclonal BIP 45 antibody immunoaffinity for 30 individual plasma samples showed that BIP 45 bound strongly to Ag(c) factor, whereas it bound weakly to the allelic Ag(g) factor. This monoclonal antibody will be useful for the detection of the two corresponding apo B species designated apo B (Ag(c) factor, BIP+) and apo B (Ag(g) factor, BIP-).

Antibodies, Monoclonal

A controlled trial of prostaglandin E1 precursor in chronic neuroleptic resistant schizophrenic patients.

The postulated deficiency of prostaglandin E1 series (PGE1) in schizophrenia has been investigated in a controlled therapeutic trial. Twenty-one inpatients with a schizophrenic illness resistant to neuroleptic drug treatments were randomly assigned to one of three treatment conditions in a blind controlled trial of dihomo-gammalinolenic acid (DHLA), a PGE1 precursor. Patients received depot neuroleptic medication and DHLA capsules, placebo depot medication and DHLA capsules, or placebo depot medication and placebo capsules. No marked treatment effects were noticed on ratings of the patients' behaviour or symptomatology, though some clinical effects were noted in dyskinetic patients. Abnormalities in red blood cell lipids were observed in the patients entering the trial, suggesting that further investigation of an EFA/prostaglandin deficiency hypothesis in schizophrenia is worth pursuing.

8,11,14-Eicosatrienoic Acid

Differential staining of different types of peripheral nerve and muscle.

We modified Ungewitter's (1951) and Beermann and Cassens' (1976) non-selective silver methods for peripheral nerve axons and their terminals by lengthening the time for the prestaining treatment of sections, adjusting the times of various stages of the staining procedures and selecting reagents with minimal chloride and sulphate impurities. These methods were applied to Bouin's fixed material embedded in wax with serial sections up to 100 micron thick, cut longitudinally. The Ungewitter modification stained sensory axons and their terminals very well but failed to give good impregnations of motor fibres. In addition, it marked intrafusal muscle fibres with a peppery silver deposit while sparing extrafusal fibres. The Beermann and Cassens method yielded excellent details of motor axons and their terminals but results were very poor on sensory fibres. Both sensory and motor methods worked regardless of whether the neural elements were mature, regenerating, or neonatal. Both methods consistently yielded pale backgrounds in these thick sections.

Acetylcholinesterase