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Biomedical subjects

J C McLachlan

Publications and source records attributed to J C McLachlan.

At least 19 recordsLinked to original sources
PubMed1999

The use of models and metaphors in developmental biology.

That models in science are of a variety of kinds and fulfil a variety of purposes has been particularly evident over the past 30 years in the field of developmental biology. At the beginning of this period, molecular and cellular mechanisms for developmental events were largely lacking, and theoretical models were developed faute de mieux. This gave way to a time in which a number of competing paradigms were present. Now, there is an increasingly detailed knowledge of underlying mechanisms, at a range of levels from genes through cells to organs and organisms. This is therefore a good time to review the usefulness of model making in general, with reference to this discipline. It is suggested that models are of two main kinds: models of structure and models of function. They fulfil three main roles, each of which operates at different stages of maturity of the field of interest. When the causes of some phenomenon are entirely mysterious, then a model may help generate hypotheses for subsequent testing. Second, when competing biological explanations are available, a model may help discriminate between hypotheses. Third, when a well-established hypothesis is available, models may facilitate use of the hypothesis. However, unlike physics, biology is stochastic and contingent, and cannot be entirely deduced from first principles. Mathematical modellers and biologists must remain in constant communication.

Animals↗
PubMed1998

Cartilaginous development of the human craniovertebral junction as visualised by a new three-dimensional computer reconstruction technique.

Serial transverse histological sections of the human craniovertebral junction (CVJ) of 4 normal human embryos (aged 45 to 58 d) and of a fetus (77 d) were used to create 3-dimensional computer models of the CVJ. The main components modelled included the chondrified basioccipital, atlas and axis, notochord, the vertebrobasilar complex and the spinal cord. Chondrification of the component parts of CVJ had already begun at 45 d (Stage 18). The odontoid process appeared to develop from a short eminence of the axis forming a third occipital condyle with the caudal end of the basioccipital. The cartilaginous anterior arch of C1 appeared at 50-53 d (Stages 20-21). Neural arches of C1 and C2 showed gradual closure, but there was still a wide posterior spina bifida in the oldest reconstructed specimen (77 d fetus). The position of the notochord was constant throughout. The normal course of the vertebral arteries was already established and the chondrified vertebral foramina showed progressive closure. The findings confirm that the odontoid process is not derived solely from the centrum of C1 and that there is a 'natural basilar invagination' of C2 during normal embryonic development. On the basis of the observed shape and developmental pattern of structures of the cartilaginous human CVJ, we suggest that certain pathologies are likely to originate during the chondrification phase of development.

Basilar Artery↗
PubMed1998

Computer-aided interactive three-dimensional reconstruction of the embryonic human heart.

Despite the fact that development of the human embryo heart is of considerable clinical importance, there is still disagreement over the process and the timing of events. It is likely that some of the conflicting accounts may have arisen from difficulties in describing and visualising 3-dimensional structures from 2-dimensional sections. To help overcome this problem and to improve our understanding of the development of the heart, we have devised techniques for the production of interactive 3D models reconstructed from serial histological sections of human embryos. Our method uses commercial software designed for the creation of 3D models and virtual reality environments. The ability to construct interactive visual images which both illustrate and communicate complex 3D information contributes to our understanding of the complex developmental changes occurring in embryogenesis.

Computer Graphics↗
PubMed1997

A proximo-distal gradient of FGF-like activity in the embryonic chick limb bud.

In a microassay for anchorage-independent growth in soft agar, NR6 cells form colonies in a dose-dependent manner in the presence of fibroblast growth factor (FGF). Using this assay system, the ability of thin sequential slices of embryonic chick limb bud to promote colony formation was investigated. A functional gradient of colony-promoting ability along the proximo-distal axis of the developing chick limb bud (stages 22-26) was observed. The highest number of colonies was observed in the presence of the most distal slices, and colony number decreased progressively at proximal levels. This gradient was specifically eliminated by the addition of anti-FGF antibody to the assay, indicating that it was caused by a functional gradient of an FGF-like molecule. Limbs of stages 21-26 were assayed: before this time limb buds are too small to slice in the proximo-distal axis in the required manner. The FGF-like gradient was observed at stages 22 to 26.

Animals↗
PubMed1997

The study of early human embryos using interactive 3-dimensional computer reconstructions.

Tracings of serial histological sections from 4 human embryos at different Carnegie stages were used to create 3-dimensional (3D) computer models of the developing heart. The models were constructed using commercially available software developed for graphic design and the production of computer generated virtual reality environments. They are available as interactive objects which can be downloaded via the World Wide Web. This simple method of 3D reconstruction offers significant advantages for understanding important events in morphological sciences.

Computer Communication Networks↗
PubMed1997

Problem-based examining: a different approach to assessment.

An attempt to achieve problem-based examining by the structured assessment of presentations is described. Students can choose to participate in the scheme in teams and then elect to use their awarded mark instead of part of the formal examination assessment. The element of choice of the study or examination method is seen as being a valuable element of the scheme. The scheme can be introduced without radical revision of existing curricula or substantial investment of staff time, and meets some of the expressed desires of the UK General Medical Council in terms of the introduction of novel methods of assessment.

Education, Medical, Undergraduate↗
PubMed1996

Embryonic chick muscle produces an FGF-like activity.

Normal and pathological formation of blood vessels is of considerable interest both in terms of basic scientific processes and clinical applications. Angiogenic events in the adult are likely to represent persistence of developmental mechanisms, and embryos are therefore a suitable experimental model for these processes. Among embryonic tissues, muscle is particularly appropriate for investigation, since it is highly vascularised from early stages. There are a number of competing explanations of how this process is controlled. Bioassays offer advantages over conventional molecular localisation techniques, in that they reveal the presence of active processed forms of the molecules under study, rather than non-processed forms, or non-translated messages. Using these techniques, we report here that embryonic chick muscle, taken from the stages at which blood vessels are forming, produces an angiogenic activity on the chick chorioallantoic membrane (CAM), and transforms NR6 cells in soft agar. Basic fibroblast growth factor (bFGF) is shown to be angiogenic on the CAM in the same way, and also transforms NR6 cells (NR6 cells lack functional epidermal growth factor/transforming growth factor-a receptors, and are believed to respond only to bFGF in this way). Anti-bFGF removes the transforming activity of the embryonic muscle. We conclude that this represents evidence that embryonic chick muscle is producing an FGF-like molecule which is capable of acting as an angiogenic agent at the appropriate times in development.

Allantois↗
PubMed1990

Identification of a novel growth factor with transforming activity secreted by individual chick embryos.

Previously we have developed a microassay for anchorage independent growth (AIG) of fibroblasts in soft agar, which can detect very small quantities of transforming growth factors (TGFs). Using this assay, we have shown that small pieces of dissected chick embryo tissue will stimulate AIG of both NR6 and NRK 49f cells, and that this property can be used to map production of growth factors with transforming activity in individual early embryos. We now show that this activity can be transferred to conditioned medium (CM) prepared using chick embryo tissue. Using two cell lines with differential responsiveness to TGFs, and by coincubating normal and heat-treated CM with trypsin, Con-A and neutralising antibodies, we show that CM contains at least two different growth factors with transforming activity. One of these is heat-stable, and stimulates colony formation in NRK 49f cells in the presence of EGF, but not in its absence. This activity corresponds to a TGF beta-like molecule. The other component is a heat-labile glycoprotein, which has TGF alpha-like properties, but does not appear to behave like known TGFs with these properties. It therefore appears to be a novel growth factor. Both activities are present from the intermediate primitive streak stage of development.

Animals↗
PubMed1990

Looping of chick embryo hearts in vitro.

Heart rudiments were removed from chick embryos at times earlier than any previously reported, and cultured in vitro, in order to test the widely reported view that looping is an intrinsic process. This view is based on experiments that are inadequately reported in certain key details. An organ culture technique was employed which combined ease of observation with good nutrient and mechanical support for the explants. A total of 23 hearts from stages before the onset of looping were examined. Hearts from as early as the six-somite stage looped normally in these experimental conditions. The view that heart looping is an intrinsic phenomenon is therefore confirmed.

Animals↗
PubMed1988

Direct demonstration of production of transforming growth factor activity by embryonic chick tissue.

The presence of transforming growth factor activity in early chick embryos was directly demonstrated by the ability of limb and tail buds to induce anchorage independent division in NRK 49 f cells. Colony number increased with limb bud number and developmental stage. Medium conditioned by tail buds contained some stimulating effect, and strongly promoted the action of other transforming growth factors.

Animals↗
PubMed1988

A microwell assay for anchorage independent cell growth.

We describe modifications of the conventional assay for anchorage independent growth of fibroblasts that enable the assay to be carried out in microwell plates, as opposed to the conventional Petri dishes. The microwell assay is a good discriminator of final EGF concentrations in the range 10-100 picograms/ml, and can be used to detect absolute amounts of EGF below 2 pg. Addition of TGF beta to EGF enhances colony formation in the microassay in the usual manner. We describe the use of this microassay to identify and map local production of transforming growth factor activity by the component pieces of individual chick embryos. Transforming activity was identified in all the stages tested (Hamburger and Hamilton stages 13-23). Highest levels were found near the mid-line of the embryo. No clear differences in the cranio-caudal axis have so far been identified. This technique will enable the spatial and temporal distribution of transforming activity throughout vertebrate embryos to be completely mapped. It seems likely that this mapping process will help elucidate the normal role of transforming growth factors in embryos.

Animals↗
PubMed1988

Limb reduplicating effects of chorio-allantoic membrane and its components.

The abilities of the chorion, the allantois, the chorio-allantoic membrane (CAM) and the yolk sac of the chick embryo to induce limb reduplications when grafted to the anterior margin of the embryonic chick limb were investigated. One chorion graft out of 27 (3.7%), two yolk sac grafts out of 30 (6.7%), five chorio-allantoic membrane grafts out of 35 (14.3%) and 26 allantois grafts out of 82 (31.7%) resulted in the formation of an extra Digit 2 or other digit of more posterior character. Allantois therefore possesses much greater ability to induce reduplications than the other membranes tested, and in view of its ease of isolation, offers a possible route for the further characterisation of this activity. The implications of these findings for theories of limb development are considered.

Allantois↗
PubMed1986

Self-assembly of structures resembling functional organs by pure populations of cells.

It is proposed that self-assembly of structures resembling organs can occur by virtue of the properties of the component cells alone. This property is derived from regional specializations of the individual component cells, and can arise in pure populations. This kind of self-assembly is distinct from the phenomenon of 'sorting out' of heterogeneous cell populations, to which this description is usually applied. It is associated with the expression of the differentiated state of the cell. Examples are drawn from the formation of blood vessels, muscles, cartilage elements, kidney, and neurectodermal derivatives.

Animals↗
PubMed1985

Stimulation of division in mouse 3T3 cells by coculture with embryonic chick limb tissue.

Two regions of the chick limb bud--the apical ectodermal ridge and the zone of polarizing activity--have been shown to influence cell division and pattern formation during normal development and following surgical manipulation. In this study, using a simple coculture system, together with autoradiography, we have shown that these morphogenetically active regions of the limb bud can stimulate quiescent 3T3 cells to initiate DNA synthesis to a significantly greater degree than comparable but morphogenetically inactive regions of the limb bud.

Animals↗