16 Wnt regulation of limb muscle differentiation.
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Journal Article↗
Biomedical subjects
P Buxton
Publications and source records attributed to P Buxton.
Growth/differentiation factor-5 (GDF-5) and skeletal development.
BACKGROUND: Growth/differentiation factor-5 (GDF-5) has been shown to be essential for normal appendicular skeletal and joint development in humans and mice. In brachypod, a Gdf-5 gene mouse mutant, the defect is first apparent during early chondrogenesis, with the cartilage blastema already reduced in size by E12.5. This defect is associated with changes in the expression of cell surface molecules. METHODS: To understand further how GDF-5 controls cartilage formation, we first mapped the expression of the Gdf-5 gene during skeletal development (please note that the abbreviation for the gene is given in italics and the abbreviation for the protein expressed by the gene is given in capital letters). Subsequently, we over-expressed GDF-5 in the developing chick embryo using a replication competent retrovirus, RCAS(BP). We determined its effects on skeletal development by histological examination and its effects on early growth by autoradiography of proliferating cells. In addition, we examined the effect of GDF-5 on chondrogenic differentiation using micromass and single cell suspension cultures of limb mesenchymal cells, RESULTS: These studies show that the Gdf-5 gene is expressed in the early cartilage condensation, the perichondrium, and the joint interzone. Over-expresSion of GDF-5 in chick limb buds, during the condensation stage or later when the skeletal elements have formed, increased the size of the affected elements. In both cases, the increase in size was associated with an increase in cell number and, at later stages, this was correlated with an increase in S-phase cells. In vitro studies showed that GDF-5 could increase cell adhesiveness, and this may be a mechanism through which GDF-5 initiates condensation formation. CONCLUSION: These studies show that GDF-5 acts at two stages of skeletal development and by two distinct mechanisms. First, GDF-5 promotes the initial stages of chondrogenesis by promoting cell adhesion, which is consistent with the expression of Gdf-5 in the cartilage condensation. Second, GDF-5 can increase the size of the skeletal elements by increasing proliferation within the epiphyseal cartilage adjacent to its expression within the joint interzone.
Animals↗
Short test of semantic and phonological fluency: normal performance, validity and test-retest reliability.
Tests of verbal fluency, whether of Semantic Fluency (SF) or Phonological Fluency (PF), are often used as a standard method of neuropsychological assessment. However, very little normative data, standardized on a UK sample, is available, and little is known about the utility of popularly used 'short-forms' of these tasks. Additionally, very little is known about verbal fluency test-retest reliability. In this report we describe the performance of N = 365 normal participants on a version of SF requiring the generation of exemplars of the category 'animals' and a version of the PF task requiring participants to generate words beginning with the letter 'B'. From this data we have derived a percentile distribution for both tasks. We also addressed the impact of sex, age, years of education and IQ upon both SF and PF performance. No sex differences were found on either the PF or the SF tasks. A significant but small correlation between age and SF, but not PF, was observed. Modest correlations between both years of education and IQ and PF and SF performance were also seen. We also report test-retest reliability scores for performance on both SF and PF tasks. Performance on the longer 'FAS' version was found to correlate highly with scores obtained using just the letter 'B'. This suggests that little additional advantage obtains from administering three-letter versions of PF. An extremely high degree of correlation between SF tasks in which participants are given 1 minute and scores obtained when participants are given 1 minute 30 seconds was also observed. Finally, in order to assist users in deciding whether a changed retest score is due to error measurement or a real effect, we calculated Standard Error of Prediction (SEP) scores.
Adult↗
Stability and plasticity of neural crest patterning and branchial arch Hox code after extensive cephalic crest rotation.
The extent to which the spatial organisation of craniofacial development is due to intrinsic properties of the neural crest is at present unclear. There is some experimental evidence supporting the concept of a prepattern established within crest while contiguous with the neural plate. In experiments in which the neural tube and premigratory crest are relocated within the branchial region, crest cells retain patterns of gene expression appropriate for their position of origin after migration into the branchial arches, resulting in skeletal abnormalities. But in apparent conflict with these findings, when crest is rerouted by late deletion of adjacent crest, infilling crest alters its pattern of gene expression to match its new location, and a normal facial skeleton results. In order to reconcile these findings thus identify processes of relevance to the course of normal development, we have performed a series of neural tube and crest rotations producing a more extensive reorganisation of cephalic crest than has been previously described. Lineage analysis using DiI labelling of crest derived from the rotated hindbrain reveals that crest does not migrate into the branchial arch it would have colonised in normal development, rather it simply populates the nearest available branchial arches. We also find that crest adjacent to the grafted region contributes to a greater number of branchial arches than it would in normal development, resulting in branchial arches containing mixed cell populations not occurring in normal development. We find that after exchange of first and third arch crest by rotation of r1-7, crest alters its expression of hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the reestablishment of the normal branchial arch Hox code. A facial skeleton in which all the normal components are present, with some additional ectopic first arch structures, is formed in this situation. In contrast, when second and third arch crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is stable, resulting in the persistence of an abnormal branchial arch Hox code and extensive defects in the hyoid skeleton. We suggest that the intrinsic properties of crest have an effect on the spatial organisation of structures derived from the branchial arches, but that exposure to increasingly novel environments within the branchial region or "community effects" within mixed populations of cells can result in alterations to crest Hox code and morphogenetic fate. In both classes of operation we find that there is a tight link between the resulting branchial arch Hox code and a particular skeletal morphology.
Animals↗
Segmentation, crest prespecification and the control of facial form.
The early development of the vertebrate head is dependent on the formation of two series of segmented structures, the rhombomeres of the hindbrain and the branchial arch series. The initial formation of these two systems is closely linked, as the principal source of branchial arch mesenchyme is the neural crest, which derives from the lateral edge of the neural plate at the time of rhombomere formation. The subsequent development of the two systems maintains a close level of integration, as specific spatial relationships between skeletal, muscle and neural elements arising from the same axial level are established. Given the level of conservation of these anatomical relationships in vertebrates, it is likely that they are a reflection of a key mechanism in early facial and pharyngeal development. One model, in part based on these findings, proposed that the neural crest acquires an axial-level specific combination of gene expression while part of the neural plate. This prepattern is then maintained throughout the crest's subsequent development. In the model, this combination of gene expression would then specify the form of the facial and pharyngeal structures that the crest would give rise to. In this review we evaluate recent evidence on whether early facial development involves a crest prespecification of this type, and conclude that it is not the case.
Animals↗
A role for midline closure in the reestablishment of dorsoventral pattern following dorsal hindbrain ablation.
The cellular and molecular study of dorsal neural tube ablation reported here demonstrates a critical role for midline closure in hindbrain repatterning. This was revealed by detailed analysis of the transcriptional response of two genes, Pax-3 and slug, during repair of the neural tube following ablation. The reexpression of Pax-3 appears to rely on a single surface ectoderm/neuroepithelial contact, while this is insufficient for reexpression of slug. In fact, slug up-regulation only occurred upon midline closure and, strikingly, corresponded to down-regulation of Pax-3. We examined whether a candidate dorsalizing molecule, Bmp-4, was responsible for this reciprocal regulation of Pax-3 and slug at midline closure. However, Bmp-4 was not reexpressed following ablation, indicating not only that it is not responsible for the observed repatterning but that it lies in regulatory pathways distinct from Pax-3 and slug. We additionally examined the expression of Pax-6, which, together with assessment of the pattern of cranial ganglia, roof plate morphology, and positioning of branchiomotor exit points, demonstrates that neural crest regeneration is accompanied by reestablishment of a normal dorsoventral pattern within the neural tube. Thus, both local and longer range patterning appears to be restored following ablation, which is reliant dorsally on midline closure of the neural tube.
Animals↗
Bowel preparation before intravenous urography: is it necessary?
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Cathartics↗
Spondyloepiphyseal dysplasia and precocious osteoarthritis in a family with an Arg75-->Cys mutation in the procollagen type II gene (COL2A1).
Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious osteoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg-->Cys mutation in one allele. The proband is a member of a large Chilean kindred presenting with chondrodysplasia of the hips, knees, shoulders, elbows, and spine associated with severe, early-onset osteoarthritis. All affected individuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the mutation segregated with the disease with a lod score of 2.2 at zero recombination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second example of an Arg-->Cys mutation in the COL2A1 gene in heritable cartilaginous disease and is the first example of a point mutation in the amino terminal region of the alpha 1(II) chain, that results in a spondyloepiphyseal dysplastic phenotype.
Adolescent↗
The location and function of respiratory fibres in the second cervical spinal cord segment: respiratory dysfunction syndrome after cervical cordotomy.
After high cervical percutaneous cordotomy for pain in malignant disease, 12 patients died during sleep at postoperative intervals between 1 and 8 days. Nine died after a first cordotomy and three after a second (contralateral) procedure. All except one had known pulmonary disease before operation. The operated segment of the spinal cord (C2) was studied histologically after death. Superposition of lesion outlines made it possible to determine those parts of the lesioned areas common to all unilateral and bilateral cases respectively. All cases dying of presumed respiratory dysfunction syndrome had lesions involving the region of the anterolateral funiculus in the C2 segment containing "pain" fibres activated from the second to fifth thoracic dermatomes. The fibres whose destruction appeared to be responsible for respiratory dysfunction syndrome were completely intermingled with ascending "pain" fibres. The possibility of these fibres being afferent in function is discussed.
Aged↗
The management of patients with an intrinsic supratentorial brain tumour.
The management of patients presenting with supratentorial glioma between 1978 and 1986 is reviewed. Complete follow-up in 517 cases was obtained. One hundred and fifty eight patients were not submitted to any form of surgery, 299 patients were biopsied and 60 patients underwent craniotomy and internal decompression. The no surgery group contained a higher proportion of patients with poor prognostic indicators than either the biopsy or craniotomy groups. The craniotomy group consisted of patients with better prognostic indicators than the biopsy group, in particular, younger age and more favourable site, type and grade of tumour. This was reflected in the difference in outcome between the groups. Median survival was 14 months in the craniotomy group, four months in the biopsy group and 2.2 months in the no surgery group. The outcome in patients with histologically proven malignant gliomas was best in those patients who received radiotherapy. The craniotomy group had a median survival of 18.5 months, a two year survival of 48% and a five year survival of 9%. The median survival following radiotherapy of those patients with proven malignant gliomas who had a biopsy was 9.5 months with a two year survival of 16% and a five year survival of 2%. These results compare favourably with studies which have adopted a more aggressive approach, suggesting that outcome is determined as much by patient selection using favourable prognostic indicators as by the treatment itself. The need for prospective trials of the management of unselected consecutive glioma patients randomizing them to conservative and radical treatment groups in order to define the role of both conventional therapy and radical therapy is discussed.
Adolescent↗
The role of needle biopsy in the management of malignant spinal compression.
With the changing management of malignant spinal cord compression there has been a reduction in numbers of patients treated by conventional laminectomy. This has resulted in a move either to the use of radiotherapy or to the use of more major surgical procedures such as the transthoracic approach. In both of these situations a more logical approach to deciding on the treatment modality to be used can be achieved by determining the histology of the lesion by percutaneous needle biopsy. This paper describes the technique of needle biopsy and presents evidence that shows that a reliable and immediate diagnosis can be achieved by the use of smear histology.
Biopsy, Needle↗
Selective necrosis of malignant gliomas in mice using photodynamic therapy.
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Aluminum↗
A case of G M2 gangliosidosis of late onset.
A case of G(M2)-gangliosidosis commencing by the age of 5 years is described, in which hyperacusis, dementia, and fits were prominent clinical features. In addition to the typical ganglioside pattern on thin layer chromatography and the presence of membranous bodies in electron microscopic studies and characteristic histology and histochemistry, there was biochemical evidence of a gross reduction in heat-labile hexosaminidase activity in white blood cells and brain. A younger unaffected sibling showed the same enzyme defect in white blood cells.
Age Factors↗