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The introduction of antimicrobial agents was a breakthrough health intervention that helped save millions of lives around the world and that provided a sense of control on the part of clinicians over host–pathogen interactions. Yet despite the concrete advances in prevention and treatment of infectious diseases, there has been a parallel surge in resistance to antimicrobials that is seriously compromising the gains made over the past century. Acknowledging the underlying mechanisms such as inappropriate use of antibiotics in humans and the agricultural applications of antibiotics for growth promotion and prophylaxis is a first and essential step to contain global antimicrobial resistance. However, it is also critical to consider in parallel the broad social, economic and political drivers and ethical significance of antimicrobial promotion in developing countries. Moreover, these socio-ethical factors constitute tangible targets against which public policy interventions can be developed to remedy growing concerns over the spread of antimicrobial resistance. In this chapter, we focus on drug promotion practices in the developing world that have important repercussions on physician prescribing habits, antimicrobial use and development of resistance. Other social factors that are endemic in developing countries – such as inadequate resources in health and education systems – can amplify erratic or suboptimal drug use. The public health consequences of, and ethical responsibilities associated with, drug promotion are substantially larger when viewed through the prism of the realities faced by persons living in developing countries. In our world of increasing urbanization and globalization, the actions of pharmaceutical companies have a global impact. Thus, their social responsibilities extend beyond developing medications for the populations of the developing world, to include socio-ethical and public health consideration for populations worldwide. Focusing on the fact that ‘what happens in the developing world does not stay in the developing world’, we propose that ethical considerations should be included as an integral part of the framework in the evaluation of appropriateness of drug promotion practices.

Much attention has been given to financial conflicts of interest (COI) in bioscience research. Yet to date, surprisingly little attention has focused on other COIs that arise in supervisor-student relations. We examine a spectrum of related situations, ranging from standard graduate supervision through to dual relationships sometimes found in research with commercial potential. We illustrate some of the less-obvious factors that can bias supervisory judgment, and situate financial COI along a spectrum of forces that are deserving of recognition. We conclude by providing two sets of recommendations: one for individual supervisors, and the other for institutions and policy-makers., [À l'origine dans / Was originally part of : ESPUM - Dép. médecine sociale et préventive - Travaux et publications]

Discussions of conflict of interest (COI) in the university have tended to focus on financial interests in the context of medical research; much less attention has been given to COI in general or to the policies that seek to manage COI. Are university COI policies accessible and understandable? To whom are these policies addressed (faculty, staff, students)? Is COI clearly defined in these policies and are procedures laid out for avoiding or remedying such situations? To begin tackling these important ethical and governance questions, our study examines the COI policies at the Group of Thirteen (G13) leading Canadian research universities. Using automated readability analysis tools and an ethical content analysis, we begin the task of comparing the strengths and weaknesses of these documents, paying particular attention to their clarity, readability, and utility in explaining and managing COI., [À l'origine dans / Was originally part of : ESPUM - Dép. médecine sociale et préventive - Travaux et publications]

Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.

A recent addition to the debate about the benefits and harms of direct-to-consumer (DTC) advertising of medicines and pharmaceuticals is a growing critique of DTC marketing and sale of genetic tests. Academic and policy literatures exploring this issue have, however, tended to focus on the sale of genetic tests, paying rather less attention to the particular implications of advertising. The globalization of broadcast media and ever increasing access to the Internet mean that public exposure to advertising for medical technologies is a reality that national regulatory bodies will be hard pressed to constrain. Working through a case study detailing Myriad Genetics' 2002 pilot advertising campaign for their BRACAnalysis genetic susceptibility test for hereditary breast and ovarian cancer, this paper highlights some of the diverse and often overlooked and unregulated approaches to DTC advertising, and the associated social, ethical and policy implications.

Aim: There are currently two dexamethasone regimes used in our nursery. We aimed to retrospectively compare the cumulative dose of dexamethasone that infants on each regime received and the requirement for further courses. Methods: Infants receiving dexamethasone between 1 January 2000 and 31 December 2004, with a gestational age of < 30 weeks or a birthweight of < 1000 g, were identified and then a chart review of these infants was undertaken. Demographic data were obtained and compared as was the total dose of dexamethasone and number of courses that each infant received. Some clinical outcome measurements were also obtained. Results: A total of 119 infants were identified. The total dexamethasone dose received was 1.92 mg/kg less for infants commencing on the 2-week course compared with the 6-week course (difference between medians, Mann-Whitney test, P = 0.005). Infants having the 2-week course had 17 days less steroid treatment (difference between medians, Mann-Whitney test, P = 0.0001). Seventeen (46%) subjects who started on a 2-week course of steroids and 18 (22%) who started on a 6-week course required at least one further course of steroids (Fisher's exact test, P = 0.01). There were no significant differences in the short-term outcome measures of neonatal chronic lung disease. Conclusion: Infants who received the 2-week course of dexamethasone had a 27% reduction in total steroid dose compared with infants receiving a 6-week course with similar short-term outcomes. However, our study was limited by its retrospective nature and possible confounding factors.

Integration of genomic data from pharmacokinetic pathways and drug targets is an emerging trend in bioinformatics, but is there a clear separation of pharmacokinetic pathways and drug targets? Should we also consider the potential interactions of endogenous substrates of drug-metabolizing enzymes with receptors and other molecular drug targets as we combine pharmacogenomic datasets? We discuss these overarching questions through a specific pharmacogenomic case study of the cytochrome P450 (CYP)2D6, serotonin and dopamine triad. Importantly, CYP2D6 may contribute to the regeneration of serotonin from 5-methoxytryptamine by virtue of its catalytic function as a 5-methoxyindolethylamine O-demethylase. Furthermore, serotonergic neurons provide a regulatory feedback on dopaminergic neurotransmission. Hence, we hypothesize that independent of its role as a pharmacokinetic gene, CYP2D6 may nuance the regulation of serotonergic and dopaminergic neurophysiology. Additionally, we reflect upon the contribution of hyperspecialization in biomedicine to the present disconnect between research on pharmacokinetics and drug targets, and the potential for remedying this important gap through informed dialogue among clinical pharmacologists, human geneticists, bioethicists and applied social scientists.

Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development—protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or ‘work’, the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context.

BACKGROUND:There has been debate on whether a global or unified field of bioethics exists. If bioethics is a unified global field, or at the very least a closely shared way of thinking, then we should expect bioethicists to behave the same way in their academic activities anywhere in the world. This paper investigates whether there is a 'global bioethics' in the sense of a unified academic community.METHODS:To address this question, we study the web-linking patterns of bioethics institutions, the citation patterns of bioethics papers and the buying patterns of bioethics books.RESULTS:All three analyses indicate that there are geographical and institutional differences in the academic behavior of bioethicists and bioethics institutions.CONCLUSION:These exploratory studies support the position that there is no unified global field of bioethics. This is a problem if the only reason is parochialism. But these regional differences are probably of less concern if one notices that bioethics comes in many not always mutually understandable dialects., Affiliation: Bryn Williams-Jones : Département de médicine sociale et préventive, Faculté de medecine, Université de Montréal

The efficiency and effectiveness of target selection and validation could be improved with accessible, standardized and integrated biological reference data sets. Such resources should be established through precompetitive approaches.

With closer interactions between academic and commercial entities the role of the university is expanding to also include knowledge transfer In the biomedical and health sciences (as well as other applied sciences), close interactions between academic and commercial entities are now common place. Funds from pharmaceutical and biotechnology companies have helped finance major bioscience projects and research centres, graduate students are receiving training in commercial laboratories, and university scientists are translating their ‘intellectual property’ by patenting their research and launching start-up companies. And this is happening with the blessing of universities, who see the commercialisation of research – and the royalties brought in from ‘technology transfer’ – as part of their new mission. The result is that no longer are universities simply places of higher learning, where academics are dedicated to teaching and research, traditionally the ‘first’ and ‘second’ missions of universities; universities now have a ‘third’ mission, to engage in knowledge transfer. Governments and research-intensive industries (such as pharma, biotech, IT), are keen to translate university research into marketable products. Facilitated by policies and laws to protect intellectual property rights and aid commercialisation, universities are transforming into ‘entrepreneurial’ institutions.1 University administrators seek to generate new funding streams, while governments see universities as drivers of technology development and economic growth. In such a climate, it should not be surprising that researchers in many disciplines are facing pressure to collaborate …

Decisions about funding health services are crucial to controlling costs in health care insurance plans, yet they encounter serious challenges from intellectual property protection—e.g., patents—of health care services. Using Myriad Genetics' commercial genetic susceptibility test for hereditary breast cancer (BRCA testing) in the context of the Canadian health insurance system as a case study, this paper applies concepts from social contract theory to help develop more just and rational approaches to health care decision making. Specifically, Daniels's and Sabin's "accountability for reasonableness" is compared to broader notions of public consultation, demonstrating that expert assessments in specific decisions must be transparent and accountable and supplemented by public con- sultation.

European airlines are now monitoring occupational exposure of aircrew to cosmic radiation, but the impacts of SW on other systems used for day-to-day operations are not considered. Future civil and military aircraft will use increasingly complex avionics and will operate in a satellite-based air-space management network. However, to maximise effectiveness of this globally interoperable system and maintain safe operations will require a greater understanding of the SW risks with increasing technology. This chapter describes the SW effects on aircraft operations and includes brief details of an ESA project to quantify those risks.

There is increasing discussion in public and academic forums about the anticipated benefits of pharmacogenomics, as well as the attendant social and ethical implications of this research. Yet there is often an implicit assumption that the benefits of pharmacogenomics are ‘just around the corner’ and will significantly outweigh the costs. Furthermore, it is argued that the associated ethical issues are not as profound as those that emerge in other areas of genetics, and that experience gained wrestling with these other issues provides ample ethical and regulatory tools to deal with any problems arising with pharmacogenomics. We contend that this vision of ethical and social issues associated with pharmacogenomics is not so clear-cut. The scientific evidence is more complex and contested than the public, academics, and policy makers, have been led to believe, and while there may be real clinical benefits from this research, they are not likely to arrive in the near future. Pharmacogenomics research is also occurring in a terrain occupied by a multitude of different and powerful actors, with diverse and often competing interests. It is therefore essential to investigate the broader social and political context, unravel the various interests pressuring for early implementation, and deconstruct the hype in order to appreciate a fuller range of ethical and social consequences associated with the current developments of pharmacogenomics.

The case study presented by Winch and Sinnott (2011) shows not only how difficult it is for clinicians and researchers to identify conflicts of interest (COI), but also how damaging it can be when there are uninformed and uncoordinated policy responses by senior administrators. The final decision by the Chief Probity Officer (CPO) proves that he lacked experience in ethical decision making, as he incorrectly weighed the harms associated with a real and apparent COI on the part of Dr. B and his technology company against the benefits of the technology for improving clinician safety and medical practice. Further, the CPO was clearly working on the assumption that the only means of managing COI was recusal; no other means of reducing the potential harm—that is, bias and lack of objectivity in the clinical studies and a subsequent loss of patient or public confidence in Dr. B and/or his technology—were envisaged. Finally, an apparent unwillingness to engage in dialogue with the Research Ethics Committee (REC) or the clinician-researcher shows an authoritarian approach on the part of the CPO that gives the message that Dr. B is engaging in misconduct because “COI is simply bad, by definition”! This approach should make one wonder whether the actual goal of the CPO’s report was not the appropriate management of COI, but instead the avoidance of potential scandal and so preservation of institutional reputation (Williams-Jones 2011). This case also highlights the problems that arise when there is a widespread lack of understanding by institutional entities—namely the Research Governance Officer (RGO), the CPO, and the REC—and clinicianresearchers of what constitutes COI and how these should be managed effectively. Dr. B and the REC were most likely operating in good faith, but with an incomplete understanding of the nature and scope of the COI—which was both real and apparent— and the risks posed for trust and confidence. By deciding there was no actual COI and by not checking with other relevant institutional agents for advice (i.e., the RGO), the REC missed an important opportunity to learn about the U.S. Institute of Medicine’s (Lo and Field 2009) recently revised definition of COI and so improve its review of Dr. B’s project. To make matters worse, the RGO, after communicating with Dr. B, did not confer with the REC Bioethical Inquiry (2012) 9:221–222 DOI 10.1007/s11673-012-9358-y

Genetic testing in the workplace is a technology both full of promise and fraught with ethical peril. Though not yet common, it is likely to become increasingly so. We survey the key arguments in favour of such testing, along with the most significant ethical worries. We further propose a set of pragmatic criteria, which, if met, would make it permissible for employers to offer (but not require) workplace genetic testing.

In seeking to clarify the concept of conflict of interest (COI) in debates about physician–industry relationships, Howard Brody (2011) highlights the extent to which the problem turns on a common p...

Savvas Saouros, Ho An Chen, Peter Simpson, Ernesto Cota, Bryn Edwards-Jones, Dominique Soldati-Favre & Stephen Matthews * Department of Biological Sciences, Wolfson Laboratories and Centre for Structural Biology, Imperial College London, South Kensington, London SW7 2AZ, U.K.; Laboratory of Molecular Biophysics, The Rex Richards Building, South Parks Road Oxford OX1 3QU, U.K.; Department Genetics and Microbiology, University of Geneva, CMU, Geneva CH-1211 4, Switzerland

The patient was an army major who, at the age of 90, had long since retired from her military nursing career. Her independence was restricted because of increasing difficulty with shoulder movements. Simple activities like washing and everyday tasks such as cooking and cleaning were becoming painful. Clinical and radiological examination revealed bilateral rotator cuff arthropathy. For her age she was in particularly good health, and we offered her a shoulder arthroscopy. She was intrigued by the concept of “keyhole surgery” and the advances of modern orthopaedic surgery. She began to indulge in …

Studies were made on the aggregation of trypsin-dissociated cells from chick embryos in the presence of Concanavalin A, a jackbean lectin, in its native tetrameric agglutinating form (n-ConA) and in a fragmented non-agglutinating form (t-ConA). The t-ConA was prepared by first trypsinizing native ConA and then subjecting the mixture to separation procedures to obtain and pool those fractions which failed completely to agglutinate cells. The presence of ConA in these fractions was demonstrated by equilibrium dialysis experiments using α-methyl- d -glycopyranoside which binds specifically to ConA. The agglutination of cells was conspicuously less in the presence of t-ConA + n-ConA than when n-ConA was added alone. The implication is that t-ConA competed with the untreated n-ConA for the same cell surface receptor sites and blocked them. The t-ConA at a final concentration of 200 μg/ml markedly inhibited the spontaneous aggregation of dissociated embryonic chick cells; the viability of these cells was unimpaired. This inhibitory effect was brought about by the t-ConA reacting with ConA sugar receptor sites. The results are correlated with current views on the possible way in which carbohydrates may be involved in cell-cell adhesion and a tentative explanation of how the t-ConA may be exerting its effect is put forward.

Secretory activity of the ventral head glands in embryos of Locustana pardalina and Locusta migratoria is necessary for inducing the moult and controlling subsequent events in late development. Continued secretory activity of the glands for a period after the moult is required for further progress in development. The development hormone released by the glands activates in turn the pleuropodial glands. The latter, in order to become fully functional, also require the continued secretory activity of the endocrine glands for a period after the moult. The enzyme-substrate system responsible for the formation of melanin does not become active until the development hormone is liberated. However, the system was present in the egg beforehand in an inactive state and it is suggested that it is held in check by an inhibiting influence. The amount of melanin deposited appears to be correlated with the amount of development hormone released.

1. A symptom of the metamorphosis of Cynthia is that the precipitous fall in the rate of oxygen consumption begins two and a half days before the spinning period.2. The rate of oxygen consumption is reduced to half the maximal rate of 1400 mm.3 O2/gm. pupal wt./hr. when spinning begins. It continues to fall throughout the spinning phase and reaches a level of 75 mm.3 O2/hr. in the early pupal stage.3. Phenylthiourea has a pronounced depressant action on the rate of oxygen consumption, the depression being proportional to the amount of this compound introduced into the blood.4. The decrease in respiration brought about by phenylthiourea coincides with the inhibition of blood phenolase activity. Possible sites of the depressant action of phenylthiourea on respiration are discussed.5. When the rate of oxygen consumption is depressed to various levels at the beginning of spinning a series of qualitatively different cocoons is produced.6. It is concluded that the pattern of spinning behaviour is delicately tun...

Both ADP and ATP markedly reduced the ability of cells from embryonic chick muscle to aggregate while rotated at 37 °C in a serum-free medium, pH 7.6. Pretreatment of the cells with ATP and ADP increased the surface charge density by 16% and 11%, respectively. The increased surface charge density persisted after thorough washing of the treated cells indicating binding of the charge-carrying nucleoside phosphates with the cell periphery. Available data do not support these changes in surface charge density as being responsible for the inhibitory effect of ATP and ADP on the embryonic chick muscle cells nor for the effects of these substances on other cell systems. A model based on the actomyosin concept of cell adhesion has been used to provide explanations for the inhibitory effect of ADP and ATP on the embryonic chick muscle cells and for the divers and opposite effects of these substances on other cell systems which have been similarly investigated.

The ability of anti-chicken smooth-muscle actomyosin γ-globulins (anti-GAM) to inhibit the aggregation of dissociated cells from the skeletal muscle and liver of chick embryos was abolished by pretreatment of the anti-GAM with either myosin or heavy meromyosin (HMM). When the same cells were treated with HMM at a concentration of 1 mg per 2 x 106 cells/ml Eagle's MEM they aggregated as readily as untreated cells. The negative electrophoretic mobility of the embryonic chick fibroblastic cells was significantly reduced by the globulin fraction of anti-GAM but not of HMM-treated anti-GAM or non-immunized rabbit serum. Anti-chicken striated muscle actomyosin γ-globulins slightly reduced negative mobility but HMM had no effect. The experiments show that the inhibitory effect on cell aggregation of anti-GAM preparations is produced by the anti-myosin antibodies. They also provide support for the theory that a surface-localized myosin-like protein has a regulatory function in cell adhesion.

Typical development in mites begins with the retraction of the epidermis from the cuticle. It is accompanied by a decrease in size and a change in shape. Atypical development also begins with a moult. But it is distinguished by regrowth, a change in shape, and an extra moult. Each moult is unique in that the epidermis divides into an outer and an inner layer. The outer layer adheres to the old cuticle. Its cells are provisionally regarded as being the source of the moulting enzymes. The inner layer retracts and persists as the true epidermis. The components of mite cuticle, according to histochemical tests, resemble those of insect cuticle. The formation of a provisional cuticle during atypical development produces the condition generally recognized as a pupal state. The moult of this provisional cuticle is primarily aimed towards synchronizing cuticle deposition with muscle development. Integration of the intermediary connecting processes, the fibrillae, with both the muscle ends and the cuticle is thus made possible.

Responses to stimuli Light In a strong beam of light the harvest mite will move directly towards the source, whereas in a weak light the tracks are at first inclined to be wavy, but as they approach the source the tracks straighten. The mite moves along the bisector of two intersecting lights of equal intensity, and when blinded on one side makes circus movements. When offered a linear gradient of light intensity the mite avoids the darkened portion and moves towards the lightest part of the field. Its movement towards sunlight is a true response to light and not to heat. A sudden decrease of light intensity produces a questing response. Temperature The sensory perception of heat is poorly developed. The mite is incapable of locating a warm tube or the body of a young live mouse. On touching a heated object it displays a well-defined response to a temperature difference of about 15° C. In a linear or concentric temperature gradient it displays avoiding reactions to low and high temperatures and appears to prefer a range extending from 15 to 26° C. Chemical stimulation The mite is repelled at a distance of 0.5 cm. from phenol, methyl phthalate, dilute ammonia, xylene and a 3 % solution of glacial acetic acid.Toluene was repugnant at 1.5 cm., whilst a mixture of amyl acetate and water repelled the mite at 5 cm. Complete indifference was shown to the odour of skin, liver, sebum and cerumen, but perspiration induced an avoiding reaction. Humidity Depletion of the water content influences the response of the mite to humidity. A desiccated mite is active in dry air and inactive in moist air, but a normal individual will settle in either moist or dry air, while avoiding saturated air. The mite requires high humidities for prolonged survival, but avoids free water. Touch Unfed mites are very sensitive to touch. The extent of stimulation by contact with each other’s bodies, which is regarded as high, immobilizes them, and it is primarily responsible for the quiescent state of a cluster of mites. When the stimulation is low, for example, when only the tarsi are in contact with a surface, the mite responds by displaying a high state of activity. A mite lightly touched will immediately quest, a response induced equally by vibrations of the substratum. Clustering The gregarious habit of the mites is primarily a response to the touch of each other’s bodies. When the humidity is within the range 95-100% R.H. light will induce the mites to climb up a rod and form a cluster at the tip. Whether or not negative geotaxis also plays a part, it is difficult to say, because the evidence suggested that the mite is independent of gravity. Sense organs There are three types of sensilla: (1) tactile sensilla, both plumose and plain; (2) peg organs; (3) minute sensory rods, principally confined to the first leg. An elliptical lens, a discoid mass of red-pigmented oily substance, and a pronounced dark pigmented cup are conspicuous features of the better developed anterior eye of each ocular area. Identification of the responses Where possible the responses of the mite to various kinds of stimuli have been identified according to a recognized scheme of classification. Behaviour in the natural environment The responses to stimuli which the mite will encounter in the natural environment, and their value with respect to acquiring a host, are discussed.

Pretreatment with p-benzoquinone and tannic acid at sub-lethal concentrations markedly reduced the aggregative competence of dissociated embryonic chick muscle cells. The degree of inhibition of aggregation by these substances at comparable concentrations was approximately the same, but the rises in the surface charge density brought about by these respective substances were widely different, being 20% with p-benzoquinone, and 84% with tannic acid. The data yielded by the electrophoretic mobility and aggregation experiments point to a lack of correlation between surface charge density and cell contact behaviour. The electrokinetic behaviour of the trypsin-dissociated embyonic chick cells at both low and high pH values indicate that their surface contains both positive and negative ionic groups. The absence of a positive component in the pH-mobility curve after treatment with p-benzoquinone at 10−4M points to the adsorbed quinones having combined with all the available positive groups at the cell periphery. Implicit in this is the suggestion that the charges carried by the adsorbed tannic acid molecules largely contribute to the 84% rise in the surface charge density. In hypotonic solutions swelling of untreated cells varied according to the tonicity of the solution. The swelling of the cells was reversible, since they reverted to their original size when returned to an isotonic solution. A perceptible swelling of quinone-treated cells occurred only in hypotonic solutions with a very low tonicity, and when returned to an isotonic solution they did not revert to their original size. These findings are in keeping with the adsorbed quinones rendering the cell periphery less extensible by cross-linking surface-located proteins. It is suggested that p-benzoquinone and tannic acid may well be producing their aggregation-inhibitory effect by blocking the movement of surface-located cell-binding components.

Skeletal muscle and liver tissue from 9-day-old chick embryos were dissociated into separate cells using 0.25 % (w/v) crude trypsin. The effect of rabbit anti-actomyosin sera on the aggregation of these cells was estimated by the gyratory shaker and turbidimetric methods. Studies were also undertaken on the ability of fluorescein isothiocyanate-labelled rabbit anti-uterine actomyosin serum (FITC-labelled anti-UAM) to stain the cell surface and on the type specificity and species specificity of rabbit anti-chicken actomyosin sera. Antisera against chicken gizzard smooth-muscle actomyosin (anti-GAM) and against chicken pectoralis striated muscle actomyosin (anti-PAM) both gave single precipitin bands with their respective actomyosins on diffusion through agar. The antisera neither reacted with their heterologous actomyosin nor with gizzard tropomyosin; they were type-specific. Serial sections of human cervix were stained in a similar pattern with both anti-UAM and anti-GAM, showing that anti-smooth muscle actomyosin sera were not species-specific. The fibrocytes of the human umbilical cord and human platelets were stained by FITC-labelled anti-UAM serum but not by labelled anti-human PAM. The aggregation of muscle and liver cells over a 24-h period in the presence of antisera against human or chicken PAM was not significantly different from the controls incubated on a gyratory shaker in Eagle's minimum essential medium (MEM) containing 10% (v/v) rabbit non-immunized serum (NIS) or calf serum. However, anti-UAM and anti-GAM inhibited both the rate of aggregation of liver and muscle cells and the size of aggregates attained in 24 h. This effect could not be simulated with specific rabbit antisera against human plasma proteins. The globulin-enriched fraction of anti-GAM markedly inhibited the aggregation of liver and muscle cells in a range of concentrations between 50 and 500 µg per 2 x 106 cells/ml Eagle's MEM. In contrast, the aggregation of cells incubated with globulin-enriched anti-PAM was similar to the controls. The addition of anti-GAM globulins at 1 or 2 h to muscle cells rotated by the turbidimetric method reduced the aggregative competence of the cells over the remainder of a 4-h period. The possibility that the inhibitory effect of anti-UAM and anti-GAM on cell aggregation is due to impurities in the antisera or to a general reaction with cell surface ATPases is discussed but, in the light of evidence, rejected in favour of a reaction between the antisera and an actomyosin of the smooth-muscle type at the cell surface.

A brain-ventral head gland system operates in embryos of Locustana pardalina and Locusta migratoria. The initiation of growth and differentiation on the termination of diapause in the egg of pardalina takes place before the ventral head glands are formed. Maximal activity in the ventral head glands coincides with the retraction of the epidermis from the cuticle. Embryos, dissected out of the egg, were kept alive in aerated sterile Ringer’s solution for up to 2 weeks during which time they progressed in their development. If post-katatrepsis embryos are ligatured between the thorax and abdomen before a * critical ‘period the moult is limited to the thorax. If ligatured immediately behind the head, the body fails to moult. Since on the termination of diapause in the egg of pardalina mitosis begins before the formation of the ventral head glands, it is suggested that in locust embryos these glands are exclusively concerned with the retraction of the epidermis from the cuticle. It is suggested that the uptake of water by the egg of pardalina in stretching the cells stimulates a growth factor which, although present throughout the diapause phase, is only capable of initiating mitosis after the diapause phase has come to an end.

Inhibitory Effect of p-Benzoquinone on the Aggregation Behaviour of Embryo-Chick Fibroblast Cells

Single-cell suspensions prepared from 9-day-old chick tissues (skeletal muscle, liver, and neural retina) were used to investigate a possible relationship between intrinsic mobilities of different cell types and their positioning behavior in mixed (heterotypic) cellular aggregates. The relative mobilities of the three cell types, determined by comparing their ability to migrate under an agarose layer, was muscle greater than liver greater than neural retina. The gyratory shaker method was employed to produce heterotypic aggregates from mixed suspensions of muscle, liver, and neural retina cells and the tissue-specific positioning of cells after 24 h in culture was determined from histological and autoradiograph sections. The hierarchy for "inside" positioning of segregated cells was muscle greater than liver greater than neural retina cells, correlating with the rate of movement of these cells in the migration assay. The implication of the results is that relative speed of movement may determine the positioning of cells in heterotypic aggregates.

Cells dissociated from embryonic chick muscle tissue using trypsin were rotated in the presence of globulin-enriched rabbit antisera against both smooth and striated muscle actomyosins originating from chicken gizzard (GAM) and pectoralis (PAM) muscles respectively. The presence of the rabbit antibodies was demonstrated using peroxidase-labelled sheep anti-rabbit λ-globulins, the enzyme-antibody conjugate being located by electron-microscope histochemistry. Anti-GAM λ-globulins reacted strongly with the plasma membrane. Judging from the complete absence of staining, λ-globulins from non-immunized rabbit serum did not interact with the membrane.When λ-globulins of sheep anti-rabbit IgG serum were applied alone, that is in the absence of pretreatment with rabbit λ-globulin, there was an observable reaction with the cell surface. Preincubation of anti-GAM with the heavy meromyosin fraction from smooth-muscle myosin inhibited the interaction of the antibodies with the membrane, as evidenced by the absence of staining. A weak positive reaction obtained with anti-PAM was due to components of the antibody preparation which were reactive with actin and not with PAM. It was concluded that a smooth-muscle myosin-like protein is an integral part of the plasma membrane of embryonic chick muscle cells.

125I-labelled sheep anti-rabbit gamma-globulin antibodies were used to locate rabbit antibodies to smooth- and striated-muscle actomyosins at the surface of trypsin-dissociated embryonic chick cells. Statistical analysis of electron microscope autoradiographs revealed that the plasma membrane of these cells was significantly labelled with both antibodies. Further tests revealed that there were a significantly greater number of antigenic sites present on the cell surface for the gizzard smooth-muscle antibodies than for those against pectoralis straited-muscle actomyosin. It was further shown that both the rate and extent of binding of the 125I-labelled smooth-muscle actomyosin antibodies to the cells were greater than for anti-straited-muscle gamma-globulins. Binding of the former was reduced to a level similar to that of 125I-NIS conjugate by preincubation of the gamma-globulins with smooth-muscle heavy meromyosin, while a simiar reduction was observed when anti-pectoralis actomyosin was treated with actin. It was concluded that actin- and myosin-like proteins must now be considered as integral components of the plasma membrane.

The trophoblast virtually isolates itself by coating its outer surface with sialomucin which seems to bring into being different but complementary devices designed to maintain pregnancy.

IT has been proposed that cell adhesion involves the participation of actomyosin-like protein located in the surface1. The theory was based mainly on the similarity between actomyosin proteins in muscle2–5 and non-muscle cells6–8, a comparison of the properties of actomyosin protein with the effects of calcium and of nucleoside phosphates9–11 on cell aggregation, and evidence indicating the presence of actomyosin-like protein at the surface of liver cells12–15. Hypothetical models have been suggested for the involvement of contractile actomyosin in inter-molecular bonding between adjacent cells16–18.