Overview of the immunization product quality control practices of vaccinators in Montérégie.
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Biomedical subjects
Publications and source records attributed to M Blackburn.
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The choice of small-scale fermentation systems contributes significantly to a successful scale-up. Creasing of flasks and the chosen shaker parameters influence the production of secondary metabolites in a strain- and even compound-specific manner. Using actinomycetes and fungi as model organisms the influence of the small-scale fermentation system on the production of various secondary metabolites is described and the effects on screening success and scale-up are considered.
Incubation with cucumber phloem exudate in vitro results in a dramatic decrease in the electrophoretic mobility of Hop stunt viroid. UV cross-linking and a combination of size exclusion and ion exchange chromatography indicate that this phenomenon reflects a previously unsuspected ability of phloem protein 2, a dimeric lectin and the most abundant component of phloem exudate, to interact with RNA. In light of its demonstrated ability to move from cell to cell via plasmodesmata as well as long distances in the phloem, our results suggest that phloem protein 2 may facilitate the systemic movement of viroids and, possibly, other RNAs in vivo.
The expression of glypican-3 (GPC3), a heparan-sulfate proteoglycan associated with the Simpson-Golabi-Behmel fetal overgrowth syndrome, was studied in normal human placental tissue and cell lines derived from human placentae. Cytotrophoblasts derived from term placentae expressed GPC3 mRNA at low levels in culture. GPC3 mRNA expression increased markedly during trophoblast differentiation. By contrast, fibroblast cell lines derived from normal placentae did not express GPC3 in culture. Similarly, choriocarcinoma cell lines derived from human placentae (BeWo, JAR, and JEG) failed to express GPC3 mRNA. In situ hybridization confirmed the localization of GPC3 mRNA to the syncytiotrophoblast. Furthermore, immunohistochemical staining of paraffin imbedded placental tissue demonstrated intense staining of the syncytiotrophoblast cell layer and less intense staining of cytotrophoblasts. No staining of mesenchymal elements was noted. These data confirm the presence of GPC3 in human placenta and suggest it is expressed by the differentiated syncytiotrophoblast at term.
Photorhabdus luminescens secretes both high molecular weight insecticidal toxin complexes and also a range of extracellular proteases into culture broth. Previous studies by others have suggested that insecticidal activity of the broth is associated with these proteases. However, by gene cloning and targeted knock-out, we have previously shown that oral insecticidal activity is associated with high molecular weight 'toxin complexes' (Tc) encoded by toxin complex or tc genes. Here we further clarify this distinction by biochemically separating the protease fractions away from the oral insecticidal activity of the Tc proteins. We purified three distinct protease fractions from the broth: one consisting of a single species of 55 kDa and two of several putatively related species of approximately 40 kDa. All of these clearly separate from the oral insecticidal activity associated with the high molecular weight Tc proteins and also show no effect on insect weight gain following injection into the haemocoel. Here we examine the substrate preferences and inhibitor profiles of these protease fractions and discuss their relationship with those previously described from other P. luminescens strains and phase variants.
After a decade of research, the parent-held Personal Child Health Record was introduced in some parts of the United Kingdom in 1991, coinciding with the enforcement of the Children Act 1989. It was designed as the main record of a child's health and development, to be used until adulthood and to be held by parents. Several Health Care Trusts have since discovered a need to maintain parallel records in the best interests of children. Barnet introduced the 'Joint Professional Record' in 1995 for selected children, such as children on the Child Protection Register. The Joint Professional Record (JPR) is a single, clinic-held, parallel record for multidisciplinary use. We undertook a programme of audit and staff seminars to develop and evaluate use of the JPR. We discuss, below, the impact of this record on professional working relationships and consider the implications of its use as a confidential record and within our policy of working in partnership with parents. In our experience, the JPR has proved a useful adjunct to clinical supervision in the arena of Child Protection and is appropriately used for children in need of protection and those with 'special needs'.
Transgenic plants expressing Bacillus thuringiensis (Bt) toxins are currently being deployed for insect control. In response to concerns about Bt resistance, we investigated a toxin secreted by a different bacterium Photorhabdus luminescens, which lives in the gut of entomophagous nematodes. In insects infected by the nematode, the bacteria are released into the insect hemocoel; the insect dies and the nematodes and bacteria replicate in the cadaver. The toxin consists of a series of four native complexes encoded by toxin complex loci tca, tcb, tcc, and tcd. Both tca and tcd encode complexes with high oral toxicity to Manduca sexta and therefore they represent potential alternatives to Bt for transgenic deployment.
Photorhabdus luminescens is a bacterium which is mutualistic with entomophagous nematodes and which secretes high-molecular-weight toxin complexes following its release into the insect hemocoel upon nematode invasion. Thus, unlike other protein toxins from Bacillus thuringiensis (delta-endotoxins and Vip's), P. luminescens toxin (Pht) normally acts from within the insect hemocoel. Unexpectedly, therefore, the toxin complex has both oral and injectable activities against a wide range of insects. We have recently fractionated the protein toxin and shown it to consist of several native complexes, the most abundant of which we have termed Toxin complex a (Tca). This complex is highly active against the lepidopteran Manduca sexta. In view of the difference in the normal mode of delivery of P. luminescens toxin and the apparent communality in the histopathological effects of other gut-active toxins from B. thuringiensis, as well as cholesterol oxidase, we were interested in investigating the effects of purified Tca protein on larvae of M. sexta. Here we report that the histopathology of the M. sexta midgut is similar to that for other novel midgut-active toxins. Following oral ingestion of Tca by M. sexta, we observed an acceleration in the blebbing of the midgut epithelium into the gut lumen and eventual lysis of the epithelium. The midgut shows a similar histopathology following injection of Tca into the insect hemocoel. These results not only show that Tca is a highly active oral insecticide but also confirm the similar histopathologies of a range of very different gut-active toxins, despite presumed differences in modes of action and/or delivery. The implications for the mode of action of Tca are discussed.
The eastern tiger swallowtail butterfly Papilio glaucus shows a striking example of Batesian mimicry. In this species, females are either wild type (yellow and black) or melanic (where most of the yellow colour is replaced by black). In order to understand how these different colour patterns are regulated, we examined the temporal order of wing pigment synthesis via precursor incorporation studies, enzyme assays, and in situ hybridisation to mRNA encoding a key enzyme, dopa decarboxylase. We show that dopa decarboxylase provides dopamine to both of the two major colour pigments, papiliochrome (yellow) and melanin (black). Interestingly, however, dopa decarboxylase activity is spatially and temporally regulated, being utilised early in presumptive yellow tissues and later in black. Further, in melanic females, both dopa decarboxylase activity and early papiliochrome synthesis are suppressed in the central forewing and this normally yellow area is later melanised. These results show that the regulation of enzyme synthesis observed in the yellow/black pattern of a single wing, is similar to that involved in melanism. We infer that dopa decarboxylase activity must be regulated in concert with downstream enzymes of either the melanin and/or the papiliochrome specific pathways, forming part of a developmental switch between yellow or black. This modification of multiple enzyme activities in concert is consistent with a model of melanisation involving coordinate regulation of the underlying synthetic pathways by a single Y-linked (female) factor.
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This annotation addresses the debate about the availability, taboos, choices and risks concerning the sexuality and abuse of young disabled people. It highlights the vulnerability of some disabled young people and discusses the dilemmas of maintaining the disabled person's dignity, safeguarding his/her independence and recognizing the need for appropriate sex education while providing protection from abuse. It is suggested that statutory agencies as well as legislation should assume greater responsibility for protecting and safeguarding the interests of disabled youngsters, some of whom may risk physical, emotional and sexual abuse beyond childhood. The manner in which sexuality and abuse are dealt with often reflects the way disabled people are regarded by the society. This paper attempts to address some of the legal and conceptual issues surrounding this area.
Recent advances in medical technology enable many children with complex disabilities to survive into adulthood and to have certain expectations of life. One of these expectations is the continuity of specialist health care in an adult setting. This paper describes a new out-patient service which aims to provide optimum care, continuity and consistency of service for adults with spina bifida and/or hydrocephalus. The need for specialist health input into this service, in order to monitor the neurological, urological and psychosocial complications often associated with spina bifida and/or hydrocephalus is recognised. In one year (1992), 86 young adults with spina bifida and/or hydrocephalus attended for annual or more frequent assessment, either independently or with their families or carers. A variety of health and social problems were treated. In response to demand, a multi-disciplinary assessment unit, which includes the services of both medical and nursing specialists, occupational and physiotherapists, psychologists and access to specialist surgical opinions has recently opened at the Chelsea and Westminster Hospital. This new service attempts to meet some of the needs described in the outpatient audit. Adults with other disabilities are requesting to use this service. A longitudinal study to monitor quality, and outcome is indicated from this initial survey.
"Earnings differentials between married and unmarried [U.S.] men have been declining since the late 1960s. We consider two possible explanations for this decline: changes in the nature of selection into marriage; and changes in role specialization within marriage. Our analysis of changes in marriage differentials within cohorts supports only a small contribution of changes in selection. There is some evidence that differences in human-capital investment between married and unmarried men have fallen over time, but this effect has apparently been largely offset by increases in the return to that human capital." This is a revised version of a paper originally presented at the 1991 Annual Meeting of the Population Association of America.
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A dinghy sailing race protocol was developed from video analysis of elite Laser class sailors competing in fairly windy (> 12 knots) national level races. A dinghy sailing ergometer was constructed for use with a 90 min protocol. Subjects watched a video of a Laser dinghy skipper sailing (on-water) according to the protocol while themselves hiking (leaning out) from the ergometer and simulating their normal on-water movements in tandem with the video. This simulation was used to examine physiological responses to dinghy sailing and factors correlated with hiking performance in 10 of Australia's top 30 Laser dinghy sailors. Simulated dinghy sailing elicited a large blood pressure response but a low rate of aerobic and anaerobic metabolism. During the 20 min upwind legs, the mean (+/- S.E.M.) systolic and diastolic blood pressures were 172 +/- 18 and 100 +/- 14 mmHg respectively, and mean arterial blood pressure (MABP) was 123 +/- 14 mmHg. Oxygen uptake during the simulated upwind legs was 1.12 +/- 0.22 1 min-1. Both blood pressure and VO2 were significantly lower during the 12 min reaching legs. The mean of the blood lactate concentrations measured 1 min following each of the upwind legs was 2.32 +/- 0.81 mM. Isometric knee extension strength (at 130 degrees) and the length to which subjects set the hiking strap on the ergometer were moderately related to upwind hiking performance (knee extension strength and upwind hiking strap tension, r = 0.62; hiking strap length and upwind righting moment, r = 0.66; both P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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