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1.
Platelets ; 33(5): 655-665, 2022 Jul 04.
Article in English | MEDLINE | ID: mdl-34986759

ABSTRACT

Burn injuries are common and often life-threatening trauma. With this trauma comes an interruption of normal hemostasis, with distinct impacts on platelets. Our interest in the relationships between burn injury and platelet function stems from two key perspectives: platelet function is a vital component of acute responses to injury, and furthermore the incidence of cardiovascular disease (CVD) is higher in burn survivors compared to the general population. This review explores the impact of burn injury on coagulation, platelet function, and the participation of platelets in immunopathology. Potential avenues of further research are explored, and consideration is given to what therapies may be appropriate for mediating post-burn thrombopathology.


Subject(s)
Blood Platelets , Cardiovascular Diseases , Blood Coagulation , Blood Platelets/physiology , Hemostasis , Humans , Platelet Function Tests
2.
RSC Adv ; 8(18): 9661-9669, 2018 Mar 05.
Article in English | MEDLINE | ID: mdl-35540841

ABSTRACT

An important histological difference between normal, uninjured dermis and scar tissue such as that found in keloid scars is the pattern (morphological architecture) in which the collagen is deposited and arranged. In the uninjured dermis, collagen bundle architecture appears randomly organized (or in a basket weave formation), whereas in pathological conditions such as keloid scar tissue, collagen bundles are often found in whorls or in a hypotrophic scar collagen is more densely packed in a parallel configuration. In the case of skin, a scar disables the dermis, leaving it weaker, stiff and with a loss of optimal functionality. The absence of objective and quantifiable assessments of collagen orientation is a major bottleneck in monitoring progression of scar therapeutics. In this article, a novel quantitative approach for analyzing collagen orientation is reported. The methodology is demonstrated using collagen produced by cells in a model scar environment and examines collagen remodeling post-TGFß stimulation in vitro. The method is shown to be reliable and effective in identifying significant coherency differences in the collagen deposited by human keloid scar cells. The technique is also compared for analysing collagen architecture in rat sections of normal, scarred skin and tendon tissue. Results demonstrate that the proposed computational method provides a fast and robust way of analyzing collagen orientation in a manner surpassing existing methods. This study establishes this methodology as a preliminary means of monitoring in vitro and in tissue treatment modalities which are expected to alter collagen morphology.

3.
Arch Dermatol Res ; 304(5): 343-51, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22566144

ABSTRACT

All patients with primary cutaneous malignant melanoma undergo surgical excision to remove the tumour, resulting in scar formation. There is marked variation in the aesthetic appearance of scars following surgery but limited knowledge about the genetic factors affecting non-keloid, surgical scar outcomes. This study aimed to investigate the role of known clinical factors and genetic polymorphisms in pigmentation and wound repair genes in non-keloid scar outcome, following melanoma excision. Participants were 202 cases who underwent a standardized scar assessment following surgical melanoma excision and provided a DNA sample. Genetic association analyses between single nucleotide polymorphisms (SNPs) from 24 candidate genes and scar outcome data were performed, controlling for relevant clinical factors. Following adjustment for multiple testing, SNP rs8110090 in TGFß1 was significantly associated with both the primary scar outcome (a combination score reflecting vascularity, height and pliability, p = 0.0002, q = 0.01) and the secondary scar outcome (a combination score reflecting vascularity, height, pliability and pigmentation, p = 0.0002, q = 0.006). The minor allele G was associated with a poorer scar outcome. Younger age, time elapsed since excision, absence of kidney failure and eczema, presence of thyroid problems and infection were also associated with poorer scar outcome and were adjusted for in the final model, along with scar site. Results from this study suggest that genes involved in wound healing may play a role in determining scar outcome. Associations observed between scar outcome and clinical factors reinforce current clinical knowledge regarding factors affecting scarring. Replication studies in larger samples are warranted and will improve our understanding of the underlying mechanisms of scarring, potentially help to identify patients at risk of poor scar outcomes.


Subject(s)
Cicatrix, Hypertrophic/genetics , Melanoma/surgery , Skin Neoplasms/surgery , Transforming Growth Factor beta1/genetics , Wound Healing/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Genotype , Humans , Male , Melanoma/genetics , Middle Aged , Polymorphism, Single Nucleotide , Skin Neoplasms/genetics , Skin Pigmentation/genetics , Surveys and Questionnaires , Treatment Outcome , Young Adult
4.
Keio J Med ; 50(1): 35-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11296663

ABSTRACT

Recent genetic analysis of the genodermatoses, in particular the palmoplantar keratodermas, has identified the important role of proteins involved in the regulation and formation of epidermal cell junctions. There are four major types of junction, of which three have been demonstrated to be important in skin, and in which component proteins such as desmoplakin and connexins are mutated in epidermal disease. These are the gap junctions, desmosomes and adherens junctions. These junctions are responsible for cell-cell adhesion and communication, key properties to maintain the normal cellular phenotype and tissue architecture.


Subject(s)
Gap Junctions/physiology , Genetic Diseases, Inborn/genetics , Skin Diseases/genetics , Humans
5.
Biochem Biophys Res Commun ; 278(3): 814-20, 2000 Nov 30.
Article in English | MEDLINE | ID: mdl-11095990

ABSTRACT

The WNT genes encode a large family of secreted glycoprotein signalling molecules important from the earliest stages of development through to the adult. We have identified a novel isoform of the recently described WNT family member, Wnt16, following analysis of chromosome 7q31 genomic sequence. We find differential organisation of Wnt16 with the generation of two mRNA isoforms, Wnt16a and Wnt16b. These isoforms differ in the composition of their 5'-UTR and first exons and show evidence of differential expression. In normal human tissues, Wnt16a is expressed at significant levels only in the pancreas, whereas Wnt16b is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. Wnt16 is one of a growing number of WNT genes showing evidence of distinct isoforms. We present evidence to suggest that these isoforms may be regulated from alternative promoters and discuss the potential functional differentiation afforded by these WNT isoforms. This may reveal subtle new mechanisms of regulation of WNT expression and function.


Subject(s)
Gene Expression Regulation , Glycoproteins/genetics , 5' Untranslated Regions/genetics , Adult , Amino Acid Sequence , Animals , Base Sequence , Exons , Female , Humans , Mice , Molecular Sequence Data , Placenta/metabolism , Polymerase Chain Reaction , Pregnancy , Protein Isoforms/genetics , RNA, Messenger/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Transcription, Genetic , Wnt Proteins
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