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PubMed1980

The Croonian lecture, 1979: Regulation of muscle contraction.

In this lecture I review briefly the history of the recognition of calcium ion as the sole regulatory factor of muscle contraction at the molecular level and how this led to the discovery of the troponin-tropomyosin system, which is the regulatory system of striated muscles of almost all deuterostomias and some protostomias. This is followed by a brief comment on the myosin-linked regulation, which plays a dominating role in many protostomian muscles. The regulatory mechanism in vertebrate smooth muscle is then discussed; the view is advanced that the leiotonin-tropomyosin system may be the only regulatory device for this muscle. Ca-binding components of troponin and smooth muscles of vertebrates are compared with modulator protein, an omnipresent Ca-binding protein of very conservative nature throughout evolution. Finally, the modes of action of Ca ion in different kinds of cell motility are discussed from an evolutionary point of view.

Actins↗
PubMed1982

The Croonian Lecture, 1981. Lampbrush chromosomes.

Lampbrush chromosomes were first observed nearly 100 years ago, and this lecture attempts a historical survey of what has been learnt from their study, particularly that over the past 30 years. There have been many controversies concerning the structure and functional significance of lampbrush chromosomes, and although their general structural layout has now, after several misconceptions, been firmly established their functional significance remains controversial. Research on lampbrush chromosomes played a significant part in establishing that chromatids in the germ lines of eukaryotic organisms are unineme in regard to DNA, and thereby exposed the C-value paradox. It also helped to establish that a DNA duplex is continuous throughout the length of a chromatid, but that the DNA/histone complex is at intervals reflected back on itself to form lateral loops. This organization, at one time thought to be a special feature of lampbrush chromosomes, now appears to be widespread in chromosomes undergoing compaction. However, despite attempts to determine the sequence organization of those portions of the DNA that are transcribed by lampbrush chromosomes, the function of these transcripts remains an open question, and the C-value paradox is still unresolved.

Animals↗
PubMed1982

The Florey Lecture, 1982. Discovery: accident or design?

The lecturer reviews the extent to which his own experiments on muscle have followed the course intended when they were planned. His observations on changes in the striation pattern were designed to reinvestigate the formation of 'contraction bands', repeatedly observed in the 19th century but neglected more recently. This phenomenon was indeed seen during active shortening, but the most important outcome consisted of two quite unexpected observations which suggested the existence of a sliding-filament system. Experiments on local activation were planned on the hypothesis that activation was conducted inward from the surface membrane along the Z line. This was apparently confirmed in the first experiments, on fibres from frog muscle, but experiments on muscle fibres from other animals, together with improvements in electron microscope technique, showed that this was a coincidence and that the Z line as such is not involved. Investigation of the transient changes of tension when a stimulated muscle fibre is suddenly shortened required a series of exploratory measurements before a useful hypothesis could be formulated. Some personal factors that have motivated scientists, including Lord Florey himself, are discussed.

Animals↗
PubMed1985

The Wellcome Foundation lecture, 1981. Nuclear magnetic resonance imaging in medicine: physical principles.

In recent years nuclear magnetic resonance (n.m.r.) has become a means of providing excellent images of the interior of the human body which are proving useful in medical practice. The development of n.m.r. imaging, much of which was pioneered in Britain, is outlined. Proton image resolution of human anatomy is comparable with X-ray computed tomography images, but without the hazard of ionizing radiation. There is improved soft tissue discrimination and pathological contrast through the basic imaging parameters of the proton density and the relaxation times T1 and T2, whose differences from one tissue to another are exploited by use of appropriate radiofrequency pulse sequences. Images may be obtained directly of transverse, coronal and sagittal sections of the head and body. Single slices or multiple slices may be imaged and imaging may be done in three dimensions. The lecture describes the more important imaging techniques and gives illustrative examples of images obtained. The efficient use of time in n.m.r. imaging is discussed, particularly mentioning the multiecho-multislice procedure and the development of real-time n.m.r. imaging. Magnetic field strengths in current use for proton n.m.r. imaging range from 0.02 to 2 T. At the lower end of the range resistive magnets are used, while for higher fields superconducting magnets are needed. A considerable improvement in image quality is obtained by use of special receiver coils.

Magnetic Resonance Spectroscopy↗
PubMed1990

The Croonian lecture, 1989. Antibodies: a paradigm for the biology of molecular recognition.

The hallmark of the antibody response to antigenic challenge is its remarkable specificity. In his Croonian Lecture in 1905, Ehrlich recognized it as a biological puzzle, but considered it inconceivable that animals could produce substances capable of specific recognition of toxins that the species had never encountered before. It took the largest part of the following 70 years to begin to understand the chemical base of the biological puzzle. Even more recently, the genetic base of the underlying events has been clarified. Unique genetic rearrangements of the DNA initiate the biological diversity of somatic cells; this provides an initial source of antigen recognition. The remarkable specificity is the result of an antigen-driven Darwinian selection of proliferating clones, operating on further diversity that is generated by a high rate of point mutations in specific genes. Although the complexity of the biological events underlying the process remain largely unknown, the knowledge gained so far provides insights into alternative approaches to the production of new antibodies.

Animals↗
PubMed1991

The Leeuwenhoek Lecture, 1991. The influence of the host on microbes that cause disease.

Microbial pathogenicity or virulence, the capacity to cause disease, depends on microbial gene products that promote infection and penetration of mucous membranes, multiplication in the tissues, interference with host defence and sickness. Formation of these virulence determinants by microbes is influenced by the environment of the host, which differs from that in laboratory cultures. Studies of microorganisms grown in vivo, and of the host's influence on the production of virulence determinants, are increasing. In most studies, however, the complex conditions in vivo are not dissected to show the influence of particular factors. In future we should define specific host factors that are responsible for producing identified virulence determinants. There are three studies which point the way. Iron limitation in vivo causes production of bacterial siderophores, outer membrane receptors and some toxins. Erythritol, a growth stimulant for brucellae, causes intense placentitis and hence abortion in cattle, sheep and pigs. Cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) sialylates a conserved component of gonococcal lipopolysaccharide (LPS), thereby rendering gonococci in patients resistant to complement-mediated killing by serum. Although the lecture uses bacteria for examples, the principle applies equally to studies of viral and fungal pathogenicity.

Animals↗
PubMed1991

The Florey Lecture, 1990. How is the cell division cycle regulated?

It is argued in this lecture that in most eukaryotic cells onset of mitosis is coupled to attainment of a critical cell mass and to completion of the previous S-phase. In fission yeast these controls operate through a regulatory gene network that activates the p34cdc2 protein kinase at mitosis. This is brought about by dephosphorylation of a tyrosine residue located in the ATP binding site of the kinase. The p34cdc2 protein kinase is also important for regulating the onset of mitosis in vertebrate cells suggesting that there is a universal control regulating mitosis in all eukaryotic cells.

Animals↗
PubMed1994

The Leeuwenhoek Lecture, 1993. Peptide vaccines: dream or reality?

Small fragments of micro-organisms which elicit protective immune responses have now been identified for several disease-causing agents. This major advance has made it possible to envisage the chemical synthesis of vaccines which could replace those in current use and may also furnish products which cannot be made by traditional methods. In my lecture I will illustrate the principles involved by describing the advances made with synthetic vaccines for foot-and-mouth disease, hepatitis B and malaria.

Animals↗
PubMed1992

An experimental course of lectures on moral treatment for mentally ill people.

By the mid 19th century, a more humanitarian approach towards the care of the mentally ill had been implemented in reforming institutions in France and Britain. This was known as 'moral treatment' and amongst its chief exponents were Pinel (Paris), Tuke (York) and Browne (Dumfries). Dr Browne perceived that the asylum attendants required education about this modality of treatment, and to this end he initiated a 'one off' course of lectures for staff at the Crichton Royal Hospital. It is considered that this experiment in nursing education is of relevance to the evolution of the role of the psychiatric nurse.

Curriculum↗
PubMed1996

Non-cognitive characteristics of medical students: entry to problem-based and lecture-based curricula.

The effectiveness of problem-based learning (PBL) versus lecture-based learning (LBL) continues to be debated all over the world. These arguments have often been based on students' cognitive measures of performance. Little emphasis has been placed on non-cognitive factors that may directly or indirectly affect the medical school performance of students in either curriculum. The purpose of this study was to (1) document possible differences in student cognitive and non-cognitive characteristics at entry between the two curricula and (2) to explore the relationships that exist between cognitive and non-cognitive factors. Data were obtained from three medical school classes (n = 281). The results indicate that students who entered the PBL curriculum at this medical school had higher total Medical College Admission Test and undergraduate grade point average than students who entered the LBL curriculum. Students who entered the PBL curriculum were also more self-sufficient and were more likely to do well in individualistic and less structured settings. There were no strong correlations between cognitive and non-cognitive variables. Before conclusions can be drawn about the effectiveness of either PBL or LBL curricula, we need to document patterns in entry characteristics to control for a priori differences that affect student performance.

Adult↗
PubMed1989

Are young adults' suicides psychologically different from those of other adults? (The Shneidman Lecture).

This Shneidman Lecture addresses the question: Are young adults' suicides psychologically different from those of other adults? Eight clusters (or patterns) as possible predictors of suicide notes and, by implication, suicide are discussed to address this question. The eight clusters are as follows: unbearable psychological pain, interpersonal relations, rejection-aggression, inability to adjust, indirect expressions, identification-egression, ego, and cognitive constriction. Comparisons between young adults (aged 18-25) and other adults indicate that young adults' suicides do differ psychologically in a number of patterns, but that considerable commonalities exist across the adult life span. The presentation emphasizes that a life span developmental perspective is essential when one is attempting to understand the suicides of young adults. A number of genuine suicide notes of young adults are presented to illustrate, from an idiographic view, what it might have been like for these individuals in the last moments of their lives.

Adolescent↗
PubMed1991

The G. L. Brown lecture. Adventures in anaesthesia.

The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex. This is shown both as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as an increase in the latency of this response. This effect is most probably a prime effect of anaesthesia since (a) it is common to all the anaesthetics used, (b) the potency of the anaesthetics is directly proportional to their lipid solubility, and (c) the effect is reversed by high ambient pressures. The major site at which information transfer is most susceptible to the action of anaesthetics is at the level of the ventrobasal thalamus, although the cells in cortical layer V also appear to have an enhanced susceptibility to anaesthetic action. This latter observation is seen both in whole animal and cortical slice preparations. None the less, the first site of synaptic transfer at which anaesthetics exert a profound effect is upon the monosynaptically generated responses of ventrobasal thalamic neurones to cuneothalamic input. A possible mechanism of action for anaesthetic agents acting at this site would be upon a hypothetical cortico-thalamic-reticular-thalamic loop with the theoretical ability to control the responsiveness of the ventrobasal thalamic cells. This action was proposed both from the activity of neurones in response to anaesthetic agents and the anatomical arrangement seen in the thalamus. The thalamic reticular nucleus is a curved sheath of cells situated between the internal capsule and the external medullary lamina, capping and bounding laterally the specific nuclei of the dorsal thalamus. There is both anatomical and physiological evidence that the thalamic reticular nucleus comprises part of the thalamic reticular formation: its cellular structure also resembles that of the brain stem regions of the reticular formation (Ramon-Moliner, 1975). Early degeneration and Golgi studies showed that ascending fibres from the medial parts of the pontine and mesencephalic components of the brain stem reticular formation innervated the thalamic reticular nucleus ventrally, by penetrating the zona incerta, and dorsally, via the intralaminar and dorsal thalamic nuclei (Scheibel & Scheibel, 1958). These observations have been confirmed and extended more recently and it appears that the major innervation of the thalamic reticular nucleus occurs via the ventral route which follows the entire course of the reticular nucleus. No fibres ascending from the dorsal column lemniscal system, the spino-cervico-lemniscal system or the spinothalamic tract have been observed to terminate within the thalamic reticular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗
PubMed1986

An investigation of the sound field above the audience in large lecture halls with a scale model.

Measurements of steady-state sound pressure levels above the audience in large lecture halls show that the classical equation for predicting the sound pressure level is not accurate. The direct field above the seats was measured on a 1:10 scale model and was found to be dependent on the incidence angle and direction of sound propagation across the audience. The reverberant field above the seats in the model was calculated by subtracting the direct field from the measured total field and was found to be dependent on the magnitude and particularly on the placement of absorption. The decrease of sound pressure level versus distance in the total field depends on the angle (controlled by absorption placement) at which the strong reflections are incident upon the audience area. Sound pressure level decreases at a fairly constant rate with distance from the sound source in both the direct and reverberant field, and the decrease rate depends strongly on the absorption placement. The lowest rate of decay occurs when the side walls are absorptive, and both the ceiling and rear wall are reflective. These consequences are discussed with respect to prediction of speech intelligibility.

Climate↗
PubMed1994

The Cochrane Lecture. The best and the enemy of the good: randomised controlled trials, uncertainty, and assessing the role of patient choice in medical decision making.

This lecture aimed to create a bridge to span the conceptual and ideological gap between randomised controlled trials and systematic observational comparisons and to reduce unwanted and unproductive polarisation. The argument, simply put, is that since randomisation alone eliminates the selection effect of therapeutic decision making, anything short of randomisation to attribute cause to consequent outcome is a waste of time. If observational comparison does have any significant part in evaluating medical outcomes, there is a grave danger of "the best", to paraphrase Voltaire, becoming "the enemy of the good". The first section aims to emphasise the advantages of randomised controlled trials. Then the nature of an essential precondition--medical uncertainty--is discussed in terms of its extent and effect. Next, the role of patient choice in medical decision making is considered, both when outcomes can safely be attributed to treatment choice and when they cannot. There may be many important situations in which choice itself affects outcome and this could mean that random comparisons give biased estimates of true therapeutic effects. In the penultimate section, the implications of this possibility both for randomised controlled trials and for outcome research is pursued and lastly there are some simple recommendations for reliable outcome research.

Consumer Behavior↗
PubMed1979

Mackellar Memorial Lecture. The veterinary profession in the EEC.

The European Economic Community was one of the major concerns of the later years of the late Campbell MacKellar. Besides being deeply involved in the affairs of the UEVP--the body representing the practising arm of the veterinary profession in Europe--he was one of the United Kingdom's representatives on the Federation of Veterinarians of the EEC over a period which saw that body emerge into an active pressure group with a real contribution to make to veterinary affairs within the Community. So said Alastair Porter in his introduction to the first MacKellar Memorial Lecture, which he gave last autumn. The following article is abridged from Mr Porter's address.

European Union↗
PubMed1975

First Geoffrey Harris Memorial lecture. Some recent developments in brain-pituitary-ovarian physiology.

Figure 14 summarizes some of the brain-pituitary-ovarian relationships which we have been discussing. Neurons in the arcuate nucleus of the hypophysiotropic area produce LRH which is secreted into the proximal capillary plexus of the hypophysio-portal system in the median eminence. LRH production is modulated in the rat and possibly also in the monkey by direct input from the preoptic region and less directly by facilitatory and inhibitory projections from the amygdala, hippocampus and midbrain. Electrophysiological evidence has been presented for "ultrashort' feedback action of LRH on arcuate neurons as well as the "short' feedback loop of LH. Gonadal steroids are pictured as feeding back directly to the pituitary and to several sites in the brain where positive and negative influences are exerted on both pituitary-ovarian function and sexual behavior. Evidence has been presented that adrenergic mechanisms influence LRH release with norepinephrine facilitatory and dopamine inhibitory to the process; dopaminergic neurons may be more intimately related to the control of prolactin secretion, and some consider dopamine and prolactin inhibiting factor to be identical. Finally, immunological methods as represented by immunohistochemistry and radioimmunoassay promise further important developments in this field in the near future. I am sure that Geoffrey Harris would have been pleased with the progress made in answering the questions which he raised in his Dale lecture.

Animals↗
PubMed1993

1993 Muriel Driver Lecture. Occupational therapy's social vision.

Occupational therapy has tremendous, unfulfilled potential. The lecture critically analyzes that potential in light of occupational therapy's social vision. The analysis is built on emerging views of occupational therapy's core philosophy of client-centered practice using the ordinary occupations of daily life as a form of therapy. Critical analysis shows that foundational features of occupational therapy are consistent with foundational features of social justice. However, analysis also shows that occupational therapy's social vision is narrowed to comply with dominant community, managerial and medical approaches to disability and aging. Given therapists' good intentions, critical analysis is unnerving, but it provides a guide for transforming practice and developing occupational therapy's potential.

Canada↗