Papers by Colin Ockleford
Advisory Committee on Pesticides : Report of the pesticides adverse health effects surveillance scheme working group (PAHES) : PAHES Final ACP7 (357/2012)
PubMed, Feb 1, 1996
The human IgG subclasses are a family of highly related yet distinct molecules. Each of these fou... more The human IgG subclasses are a family of highly related yet distinct molecules. Each of these four subclasses performs a discrete function within the human immune system. Previous studies have shown that one of these molecules, hIgG2, may be discriminated against in transport across the human placenta. We have aimed to elucidate the mechanism of this discrimination in order to gain a more comprehensive understanding of the process of transport of immunoglobulin across the human placenta. We have used a combination of immunocyctochemical localisation and biochemical analysis to detail the behaviour of hIgG2. Confocal laser scanning microscopy was used to compare the localisation of hIgG1 (chosen as representative of the efficiently transported subclasses) and hIgG2 in term and first trimester chorionic villi. Complementary evidence was provided from immunoblot analysis of isolated placental coated vesicles. The data presented here suggest that the hIgG2 is transported into the syncytiotrophoblast and appears to accumulate in the stroma of the villi. This leads us to the hypothesis that the fetal capillary endothelium is the cellular impediment to the transport of hIgG2 into the fetal circulation.
The allo-epi-endothelial lining of the intervillous space
Placenta, Dec 1, 2010
An unusual monolayer of cells lines the interface between the basal plate and the intervillous sp... more An unusual monolayer of cells lines the interface between the basal plate and the intervillous space in human term placenta but not the chorionic villi. Our recent descriptions of it are based on advanced microscopy, phenotyping and cytogenetic approaches. The papers show that the layer is partly epithelial (ectoderm) and partly endothelial (mesoderm): it is partly derived from the fetus and partly from the mother. This first accurate description of a naturally occurring human allo-epi-endothelium (monolayer of cells derived from two embryological germ layers and two individuals) is of interest in anatomy, obstetrics and gynaecology, developmental biology, histology and immunology. The most extensive evidence for this mosaic applies to the intervillous space lining layer of the basal plate where the endothelial proportion is of the order of 50%; it extends throughout central, intermediate and peripheral parts of the basal plate and is a consistent feature of the intervillous space lining of the chorionic plate also. Its presence lining chorionic plate is noteworthy as it includes the furthest parts of the sinus from the supplying and draining vessels which are endothelial lined.
In situ Hybridization and Immunofluoflurescent Localization of tPA,uPa,PAI-1 and PAI-2 in Human and Rhesus Monkey Placentae
The localization and distribution of mRNAs and antigens of tissue type (t) and urokinase type (u)... more The localization and distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activator (PA) plus their corresponding inhibitors type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridization and immunofluorencence. We have demonstrated that (1) plasminogen activators (tPA and uPA), and their inhibitors (PAI-1 and PAI-2) for both mRNAs and proteins in most cases, co-localized in the same areas, but with different extent, in human and rhesus monkey placentae; (2) All the molecules, tPA, uPA, PAI-1, and PAI-2 and their mRNAs were identified in the wall of blood vessels of villi stem and decidua, extravillous cytotrophoblast cells of basal plate between Rohr's and Nitabuch's striae, trophoblast shell and decidual gland cells as well as cytotrophoblast cells of villi. However, tPA and PAI-1 were found to be more evident in the regions adjacent to abscission planes from the maternal tissue, while uPA and PAI-2 concentrated mainly in villous trophoblast and extravillous trophoblast cells; (3) Distribution of the mRNAs of the 4 genes is generally consistent with the immunofluorescent pattern of the corresponding antigens, however, no expression of the mRNAs, but their proteins was observed in syncytiotrophoblast cells of villi; (4) The patterm of distribution and synthesis of the activators and inhibitors coincides with the distribution of fibrin-like molecules; (5) The distribution pattern of the mRNAs and their proteins was similar in monkey and human placentae, no spcies-difference was demonstrated. The data suggest that the activators and the inhibitors described here interact at a variety of crucial physiological stages of pregnancy. They may interact in tightly restricted locations to the matrix fibrinoids in rather short ranges and at specific times, particularly during early and late pregnancy, to promote healthy gestation. It is possible that failure of the local control over the system may be important in failure of implantation and premature rupture of membranes. We now propose that the location of these molecules gives the system potential in the control over establishment of uterofetal blood circulation and placentation in the first two trimesters of gestation and abscission during the third stage of labour and predict a role in the pathology of abrupio placenta and retained placental products.
Morphological Marker of Gentamicin Resistance
The Lancet, Jul 1, 1977
tPA, uPA, PAI-1和 PAI-2在人和恒河猴胎盘中的原位杂交和荧光免疫定位(英文)
发育与生殖生物学报：英文版, 2000
用原位杂交和荧光免疫定位方法研究了组织型（t）和尿激酶型（u）纤溶酶激活因子tPA、uPA和相应的抑制因子PAI－1、PAI－2在人和恒河猴胎盘中的定位和分布。结果表明：（1）激活因子tPA、u... more 用原位杂交和荧光免疫定位方法研究了组织型（t）和尿激酶型（u）纤溶酶激活因子tPA、uPA和相应的抑制因子PAI－1、PAI－2在人和恒河猴胎盘中的定位和分布。结果表明：（1）激活因子tPA、uPA(Fig.1&4)和抑制因子PAI－1（Fig.2)、PAI－2（Fig.3)一般都在不同程度上定位于两者胎盘的相同部位；（2）它们主要分布在绒毛干和蜕膜的血管壁、Rohr′s和Nitabuch′s纹间的基盘外绒毛滋养层细胞、滋养壳、蜕膜细胞和脱体细胞。并且发现，tPA和它的抑制因绒毛滋养层和外绒毛滋养细胞中；（3）激活因子和抑制因子的mRNA和抑制因子PAI－1更集中在绒毛滋养层和外绒毛滋养细胞中；（3）激活因子和抑制因子的mRNA和蛋白的定位和分布基本上一致，但是、在绒毛核体滋养层细胞上未发现其mRNA表达，却有很强的免疫荧光的分布；（4）激活因子和抑制因子合成和分布部位与其作用底物，即纤蛋白类分子的产生部位一致；（5）未发现上述分子在人和恒河猴胎盘分布上的不同。上述实验结果说明，在妊娠折各个阶段PA和它的抑制因子协同表达，局限在范围很小的特定产生底物的区域。它们的相互作用可能是维持正常妊娠所必需。在妊娠早期对子宫－胎儿血液循环系统的建立和胎盘的形成、在分娩期对母体与胎儿的分离机制中起重要作用。PA系统调控的局部失调可能会导致胎泡着床失败，胎膜早破引起流产或早产。上述分子的表达产物有可能成为预见妊娠生理状态的重要标记。
Journal of Cell Science, Jun 1, 1976
There is a surface structure on the coated vesicles of human placenta. Some features of this stru... more There is a surface structure on the coated vesicles of human placenta. Some features of this structure have been examined. Measurements of the polygonal network seen in surface views have been made and compared with measurements of structures projecting from vesicle walls in median sections. A 3-dimensional reconstruction of the vesicle shows the pattern to be one of raised ridges. Use of a goniometer to tilt the specimens has confirmed the assumption that both types of image obtained are from one structure. Although it is usually the case that vesicles are approximately spherical, some are definitely irregularly shaped. For this reason it is suggested that the walls of the polygons need not always be packed into a structure with a regular and precisely maintained pattern. Consideration of the surface structure in the light of current understanding of the cell membrane as a dynamic system leads to a possible explanation of the process of vesicle formation in this context and of the selective nature of uptake by micropinocytosis.
Journal of Cell Science, Dec 1, 1974
A study of cytokinesis in the heliozoan Actinophrys sol has been made using low-temperature treat... more A study of cytokinesis in the heliozoan Actinophrys sol has been made using low-temperature treatments, antimitotic drugs, cytochalasin B, light microscopy and electron microscopy. It reveals that microtubular axopodia remain extended during cell division and play a major role in it. Data indicate that when organisms are attached to the bases of culture dishes the normal locomotive mechanism of the presumptive daughter cells pulls them apart. However, when Actinophrys are floating freely in their culture medium, they are still able to undertake division. In this situation interactions between axopodia from opposite daughter cell bodies appear to facilitate the movement apart of the prospective daughter cells. The present study and other published accounts indicate that a type of cytokinesis exists which is not explicable in terms of the 'contractile ring' or 'fusing vesicle' theories. To account for these observations a 'barge pole' model of division is suggested.
Fetal capillary endothelium as an impediment to the transport of the human IgG2 subclass across the human placenta?
Placenta, Oct 1, 1994
A ‘top stage’ scanning ultrastructural study of healthy and premalignant trophoblast
Placenta, Sep 1, 1989
Immunofluorescence and Nomarski Differential Interference Contrast Microscopy of Normal and Hydatidiform Molar Human-Placenta
The Uptake of Igg by Human Chorionic Villi
Personal Reminiscences of The Nobel Prize winner R.G.Edwards.:Novel technique to routine medical practice
Scientific Opinion addressing the state of the science on risk assessment of plant protection products for non-target terrestrial plants
Following a request from the European Food Safety Authority, the Panel on Plant Protection Produc... more Following a request from the European Food Safety Authority, the Panel on Plant Protection Products and their Residues developed an opinion on the science to support the development of a risk assessment scheme of plant (crop) protection products on non-target terrestrial plants (NTTPs). This scientific opinion is largely a literature review on the most up-to-date knowledge of factors influencing phytotoxicity testing and risk assessment of NTTPs. Specific protection goals (SPGs) were defined for off-field, in-field and endangered species. SPGs are closely linked to ecosystem services and functions, and include maintaining provision of water regulation, food web support, aesthetic values, genetic resources and biodiversity. Gaps were identified in standard guidelines currently used in lower tier testing (tier I/II). In these guidelines, tests are conducted at the seedling/juvenile stage using mostly annual crops, and effects are recorded at the juvenile/vegetative stage under greenhouse conditions with plants grown individually or in monoculture. Endpoints measured do not include the overall effect on the whole life cycle (germinating seeds, seedling, juvenile stages, flowering, and seed production and germinability). It is also noted that it is unknown whether the following groups of organisms are covered by the plant risk assessment as it is carried out now: ferns, mosses, liverworts, hornworts, horsetails, lichens or woody species. In terms of exposure, droplet drift is considered to be the most important factor for off-field emissions to non-target areas. Models are available to calculate loadings from spray drift. Higher tier assessment is not required if the risk based on the tier II level can be managed by risk mitigation measures. When required, higher tier tests should be conducted under more realistic conditions. They may include additional laboratory/greenhouse tests (e.g. to measure reproductive endpoints or species interactions), microcosms or field experiments with experimentally or already established species. Other issues were considered, including exposure to mixtures, adjuvants, co-formulants and metabolites. Recommendations for the improvement of current guidelines and the elaboration of new guidelines and risk assessment schemes are provided.
Microinjection of Human Chorionic Villi
Scientific Opinion on the relevance of dissimilar mode of action and its appropriate application for cumulative risk assessment of pesticides residues in food
The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and their ... more The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and their Residues (PPR Panel) to develop a Scientific Opinion on the relevance of dissimilar mode of action and its appropriate application for cumulative risk assessment of pesticides residues in food. The present opinion was preceded by three previous opinions of the PPR Panel (EFSA, 2008, 2009, 2013). The purpose of the present opinion was to assess the relevance of dissimilar modes of action (MoA) for cumulative risk assessment, to evaluate the existing methods for assessing chemicals acting by dissimilar MoA and to identify which methods need to be considered. The PPR Panel restricted its considerations of pesticide combinations with dissimilar modes of action to substances that produce a common adverse effect on the same organ/system. The PPR Panel noted that there is no case documented in the scientific literature where independent action provided more conservative predictions of combination effects than dose addition, and where at the same time independent action also produced accurate predictions. The use of independent action as an assessment concept for combination effects requires demonstration that modes of action of individual substances in a mixture are strictly independent, a condition that can rarely be met in practice. The PPR Panel also noted that there is no cumulative risk assessment method derived from independent action. The PPR Panel therefore recommends using cumulative risk assessment methods derived from dose addition also for the assessment of mixtures of pesticides with dissimilar modes of action, provided they produce a common adverse outcome. Pesticides that produce common adverse outcomes on the same target organ/system should be grouped together in CAGs, and their combined effects assessed by using the concept of dose addition as a pragmatic and conservative default approach for the purpose of assessing cumulative risk in relation to MRL setting or risk assessment of chemical mixtures in practice.
Oxygen Transport in Biological Systems:Modelling of Pathways from Environment to Cell
Journal of Anatomy, Dec 1, 1994
Immunolabelling of caveolin-3 in striated muscle cells of rats and mice
A confocal laser scanning microscopy analysis of differentially expressed cytokeratins in pre-eclamptic and healthy term placental basal plate tissue
EFSA performs environmental risk assessments (ERAs) for single potential stressors such as plant ... more EFSA performs environmental risk assessments (ERAs) for single potential stressors such as plant protection products, genetically modified organisms and feed additives and for invasive alien species that are harmful for plant health. In this risk assessment domain, the EFSA Scientific Committee recognises the importance of more integrated ERAs considering both the local and landscape scales, as well as the possible co-occurrence of multiple potential stressors that fall under the remit of EFSA, which are important when addressing ecological recovery. In this scientific opinion, the Scientific Committee gathered scientific knowledge on the potential for the recovery of non-target organisms for the further development of ERA. Current EFSA guidance documents and opinions were reviewed on how ecological recovery is addressed in ERA schemes. In addition, this scientific opinion is based on expert knowledge and data retrieved from the literature. Finally, the information presented in this opinion was reviewed by experts from the relevant EFSA Panels, European risk assessment bodies and through an open consultation requesting input from stakeholders. A conceptual framework was developed to address ecological recovery for any assessed products, and invasive alien species that are harmful for plant health. This framework proposes an integrative approach based on well-defined specific protection goals, scientific knowledge derived by means of experimentation, modelling and monitoring, and the selection of focal taxa, communities, processes and landscapes to develop environmental scenarios to allow the assessment of recovery of organisms and ecological processes at relevant spatial and temporal scales.
Uploads
Papers by Colin Ockleford