Hypertrophic scars are painful and unsightly scars frequently resulting from dermal trauma and characterised by excessive collagen. The application of silicone gel sheeting is an effective treatment for these scars. Proton Induced X-Ray Emission, Elastic (Non-Rutherford) Backscattering and Instrumental Neutron Activation were used to determine the compositional changes in the silicone gel sheeting and the skin resulting from contact of the gel with scarred and unscarred skin, and found that although in vitro tests on split skin and in vivo tests using unscarred tissue causes the skin to absorb Si (an essential constituent of collagen) from the silicone gel sheeting; in vivo tests on hypertrophic scar and control tissue show the reverse: silicone gel sheeting absorbs Si from hypertrophic scars against the concentration gradient. It is believed that this is an important factor in the success of the treatment of hypertrophic scars by silicone gel sheeting. The major, minor and trace element composition was determined for a total of 35 skin samples including breast, abdominal and hypertrophic scar tissue, comparing dermis and epidermis for these samples. Some split skin samples were also included. The hypertrophic scar tissue is characterised by enhanced Si content, with 3wt% compared with an average of 2wt% for the unscarred tissue. A pilot clinical trial was then conducted on 20 unscarred volunteers as controls over a week, and 9 volunteers with hypertrophic scars (clinical gel) over a three month period with silicone gel sheeting nominally used according to a strict protocol. Two subjects did not complete the trial, and there was evidence of non-compliance for at least three others. However, without excluding any data, we have observed a significant increase (10+/-1%) in Si content of the silicone gel sheeting in contact with hypertrophic scar over the controls. Significant composition differences between the dermis and the epidermis were observed as expected. Differences between the composition of scarred and unscarred tissue were not large. Significant increases in the average elemental composition were seen between the clinical gel compared to the unused gel for the elements: Cl, K, Ca, Fe and Ag providing further evidence that the gel absorbs elements from the scar tissue.

No description available.

No description available.

No description available.

The natural history of scar maturation in humans has been described by Bond et al. (2008b) in a male European Continental Ancestry Group (ECAG). It is important that the natural history of scar maturation in humans is established for all skin types. This study therefore aims to describe clinically and histologically the maturation of scars in male volunteers from the African Continental Ancestry Group (ACAG).This study was performed as a single centre, methodology trial. Three incisions and a punch biopsy were carried out on each arm. Monthly assessments of the resultant scars included: investigator scar assessments; scar photography; VAS scoring by an Independent External Scar Assessment Panel; and objective measures of colour and scar mechanics. At various time points scars were excised for histology. Sixty male subjects of African Continental Ancestry between the ages of 18-56 years were recruited to take part in the study. The clinical appearance of a scar in the ACAG improves with time. Scar colour mismatch decreases and the mechanical properties of scars improve with time. Scar width increased over the 12 months. With the exception of scar contour and scar redness, a steady state was not achieved. Volunteer skin type was shown to influence the resulting scar appearance and not age. The histology of scar maturation in the ACAG over 12 months was described and scars classified into three groups each displaying a different rate of longitudinal progression of scar maturation. The process of collagen maturation is still ongoing at month 12; many scars demonstrated a prolonged high turnover state of collagen synthesis and degradation, rete ridge restoration and angiogenesis were still ongoing with persistent inflammation identified in scars up to Month 12. There is a strong correlation shown between the Clinical VAS scores and the Histology VAS scores for the papillary dermis which is of better quality than the reticular dermis. There is some evidence that young people (ACAG) and volunteers with darker skin have poorer scar histology. The spectrophotometry data indicated that the Fitzpatrick Skin Type Classification is a useful method of classifying the varying skin colours of this group of volunteers. In conclusion, scar maturation in the ACAG occurs as a series of defined macroscopic and microscopic stages over the course of 1 year. The process of scar maturation is not complete at 12 months. All scars showed evidence of improvement over the course of the study influenced in part by volunteer skin type and age. Results suggest that scar maturation in this study group occurs at a different rate and is of a different quality, compared to current knowledge of scar maturation in the ECAG.

Yes / Coronin7 (CRN7) stabilizes F-actin and is a regulator of processes associated with the actin cytoskeleton. Its loss leads to defects in phagocytosis, motility and development. It harbors a CRIB (Cdc42- and Rac-interactive binding) domain in each of its WD repeat domains which bind to Rac GTPases preferably in their GDP-loaded forms. Expression of wild type CRN7 in CRN7 deficient cells rescued these defects, whereas proteins with mutations in the CRIB motifs which were associated with altered Rac binding were effective to varying degrees. The presence of one functional CRIB was sufficient to reestablish phagocytosis, cell motility and development. Furthermore, by molecular modeling and mutational analysis we identified the contact regions between CRN7 and the GTPases. We also identified WASP, SCAR and PAKa as downstream effectors in phagocytosis, development and cell surface adhesion, respectively, since ectopic expression rescued these functions.

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No description available.

Soybean (Glycine max) is an important crop in the world in terms of total production and usage. It is also among the least diverse species. The main objectives of the present study were 1) to determine differences between ISSR and RAPD marker systems in detecting genetic variation in soybeans and 2) to identify and characterize accession- diagnostic molecular markers in G. max accessions. Genomic DNAs from 108 G. max accessions from 11 different gene pools were analyzed using several ISSR and RAPD primers. The levels of polymorphic loci detected with the two marker systems were in general moderate and similar.. Overall, 82% of genetic distance values were above 0.40 based on ISSR analysis. However, RAPD data revealed that the accessions from different countries are closely related with 64% genetic distance values below 0.40. The dendrograms constructed with ISSR data revealed that the South Korean accessions formed an out-group while the RAPD analysis showed that accessions from Sweden were separate from the other 10 gene pools. One variety-diagnostic marker generated with ISSR 5 primer was identified in the accession Kao Chien Tao from China. This marker was cloned, and sequenced. Although RAPD and ISSR marker systems detected similar levels of genetic variability, they target different regions of the soybean genome, resulting in different clustering of the 11 gene pools indicating different genetic relatedness among them. This finding demonstrates the usefulness of both marker systems in assessing diversity and relatedness among Glycine max gene pools.

Unlike other regenerative organs such as the liver, the adult mammalian heart does not regenerate tissue lost following injury such as myocardial infarction (MI). Instead a non-contractile fibrous scar develops that in the longer term leads to the development of heart failure (HF). In contrast to the adult, neonatal mammals, including mice and man, retain potent cardiac regenerative capacities and can replace myocardium lost following injury. Understanding the mechanisms underlying scar free repair in the neonate may help in development of new approaches to reduce the impact of myocardial injury in adults. In this thesis MI was induced by coronary artery ligation in mice at post-natal day 1 (P1). Novel electrocardiogram gated high resolution cardiac ultrasound was developed to permit non-invasive confirmation of injury 1 day later and regeneration 21 days later by loss, then restoration, of contractile function. Macrophages (MФ) play important roles in organ growth and homeostasis, and are required for scar-free regeneration of the neonatal mouse heart following MI. WNTs are secreted lipophilic proteins with multiple roles in development. MФ-derived WNTs are essential for scar free tissue regeneration following injury in the kidney, liver, and gut, but their role in the heart is unknown. The primary aim of this thesis was to investigate the role of MФ, and in particular MФ-derived WNTs in determining normal growth of the myocardium from neonate to adult and also in regeneration of the neonatal heart following injury. In wild-type neonatal mouse hearts, Csf1r-expressing cells density (mostly macrophages) was consistent across all time points studied. Three populations of resident cardiac mononuclear phagocytes were identified by flow cytometry: F4/80hi, CD11blo, Ly6C-ve - F4/80lo, CD11bhi, Ly6C-ve - F4/80lo, CD11bhi, Ly6C+ve. F4/80hi, CD11blo, Ly6C-ve cells were hypothesised to correspond to yolk-sac derived mononuclear phagocytes and F4/80lo, CD11bhi, Ly6C-ve - F4/80lo, CD11bhi, Ly6C+ve to foetal liver/bone marrow derived mononuclear phagocytes. Three phases of myocardial growth were identified by ultrasound and histological techniques: hyperplastic (P2-P8, with increased Ki67 and cardiac troponin immunopositive cells), hypertrophic/reorganisation (P8-P21, with increasing cardiomyocyte size and no change in left ventricle wall thickness), and finally hypertrophic solely (P21-P42, with increasing cardiomyocyte size and left ventricle wall thickness). Average coronary vessel size was shown to decrease between P2 and P8 whilst vessel density was increased. The number of α-smooth muscle actin (αSMA) coated vessels greatly increased between P8 and P42, indicating vessel maturation. Throughout all phases cardiac systolic function was maintained at steady state. Diastolic function was however shown to mature from a foetal to an adult pattern between P2 and P8, with reversal of the E:A wave ratio on Doppler ultrasound. In mice globally deficient in MФ due to a germline knock-out of the Csf1r gene (Csf1rnull mice), both body and heart weights were decreased from P7 onwards. The number of proliferating (Ki67+ve) cardiomyocytes at P1 and P7 was unchanged in Csf1r-null mice but there was a trend towards decreased cardiomyocyte size at P7, suggesting an influence on hypertrophic rather than hyperplastic growth of the myocardium. There was also a trend for slowed vascular network maturation, with a delay in the shift from large to smaller vessels in hearts from Csf1r-null mice. In mice with MФ-directed (Csf1r-icre mediated) depletion of Porcupine (Porcn), a gene encoding an enzyme required for WNT acylation and secretion cardiac growth, vascularisation, fibrosis and function were all similar in Cre-ve and Cre+ve animals until P41, when cardiomyocyte size and cardiac systolic function were both significantly increased in Cre+ve animals. However, the underlying mechanism is unknown. In the neonatal mice, Csf1r expressing cells, mostly MФ, were identified in association with regenerating myocardium after induction of MI at P1. Flow cytometry data showed that by P7 the putative resident yolk-sac derived population had mostly disappeared from the heart and was replaced by F4/80lo cells, similar to the pattern reported in the adult. In the regenerating myocardium, Axin2 expression was increased consistent with activation of canonical Wnt signalling. Expression of Wnt5b and Fzd2 receptor, both associated with fibrosis, was significantly increased relative to age matched uninjured hearts. MФ-directed depletion of Porcn did not influence either the functional decrease at day 1 or recovery at day 21 following induction of MI at P1. Coronary re-vascularisation was also unaffected by the genotype. However, retention of intra-myocardial fibrosis (picrosirius red staining) was significantly increased in hearts at day 21 post-MI from mice with MФ-directed depletion of Porcn. MФ-derived WNTs are therefore required for scar-free wound healing in the heart, as they are in the liver and the kidney where they regulate matrix metalloproteinase activity. In summary, novel ECG-gated high-resolution in vivo ultrasound developed in this project has allowed characterisation of cardiac structure and function during early post-natal growth and following injury and regeneration in neonatal mice. The resident MФ population of the heart is established pre-natally, and may play a role in determining maturation of the developing vascular network, although this does not involve MФ-derived Wnt signalling. Following MI, the MФ population may expand from bone marrow cells and MФ accumulate around the regenerating tissue. MФ derived WNTs are not required for regeneration of the neonatal myocardium but do have a role in ensuring scar free wound healing and this merits further investigation.