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Biomedical subjects

E J Wood

Publications and source records attributed to E J Wood.

At least 19 recordsLinked to original sources
PubMed2004

Macrophages restrain contraction of an in vitro wound healing model.

Significant numbers of macrophages are present during all stages of dermal wound repair, but the functional significance of these macrophages, especially during the later contraction and remodelling stages of repair, remains unclear. We investigated the effect of macrophages on wound contraction using a novel in vitro model based upon the contracting dermal equivalent (DE). Macrophages were found to reversibly restrain DE contraction, a rapid and sustained effect that was enhanced by lipolysaccharide (LPS) treatment of macrophages and partially inhibited by hydrocortisone. Prolonged inhibition of contraction was strongly correlated with an inhibition of fibroblast proliferation. The rapid contraction-inhibiting effect of the macrophages was mediated through activation of protein kinase C (PKC). These results suggest that inflammatory macrophages restrain the later stages of wound repair, namely matrix contraction and remodeling. The novel in vitro model established here provides a useful system for examining fibroblast-macrophage interactions in the healing wound.

Adolescent↗
PubMed2002

Pathological scarring: strategic interventions.

Aberrant cutaneous scar formation is a substantial cause of postoperative morbidity. There is at present no clear consensus on the best way to prevent or treat such scarring, although recently there has been considerable progress in developing an understanding of the mechanisms of tissue repair and scarring. We carried out a literature review using Medline to establish the current understanding of the key events occurring during tissue repair and to identify potential causes of scarring. We now review the key events during tissue repair and the pathogenesis of fibroproliferative disease. Tissue repair is achieved through a multistranded, elegantly coordinated process within which the balance between synthesis and breakdown of matrix is upset during fibrotic disease. Scars form because the signals directing tissue repair are not correctly terminated, and while the initiation and propagation of repair is well understood the signals that direct its cessation have yet to be elucidated.

Cicatrix↗
PubMed2001

The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro.

The effects of chitin [(1 --> 4)-2-acetamido-2-deoxy-beta-D-glucan] and its partially deacetylated derivatives, chitosans, on the proliferation of human dermal fibroblasts and keratinocytes were examined in vitro. Chitosans with relatively high degrees of deacetylation strongly stimulated fibroblast proliferation while samples with lower levels of deacetylation showed less activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chitosan chloride was further evaluated using cultures of fibroblasts derived from a range of human donors. Some fibroblast cultures produced a positive mitogenic response to CL313A treatment with proliferation rates being increased by approximately 50% over the control level at an initial concentration of 50 microg/ml, whilst others showed no stimulation of proliferation or even a slight inhibition (< 10%). The stimulatory effect on fibroblast proliferation required the presence of serum in the culture medium suggesting that the chitosan may be interacting with growth factors present in the serum and potentiating their effect. In contrast to the stimulatory effects on fibroblasts, fraction CL313A inhibited human keratinocyte mitogenesis with up to 40% inhibition of proliferation being observed at 50 microg/ml. In general highly deacetylated chitosans were more active than those with a lower degree of deacetylation. These data demonstrate that highly deacetylated chitosans can modulate human skin cell mitogenesis in vitro. Analysis of their effects on cells in culture may be useful as a screen for their potential activity in vivo as wound healing agents, although in the case of fibroblasts it is important to select appropriate strains of cells for use in the screen.

Biocompatible Materials↗
PubMed2001

Biochemistry and molecular biology teaching over the past 50 years.

The revolution in molecular biology that began nearly 50 years ago has had an enormous impact in the lab, but it also triggered a quieter revolution in undergraduate teaching. How has it affected the content and teaching methodology of undergraduate courses, and is the training that students now receive in the molecular life sciences appropriate to their future career paths?

Biochemistry↗
PubMed2001

4-(N-hydroxyphenyl)retinamide can selectively induce apoptosis in human epidermoid carcinoma cells but not in normal dermal fibroblasts.

The retinoid 4-(N-hydroxyphenyl)retinamide (4HPR, fenretinide) has both growth inhibitory and apoptosis-inducing effects on a number of cancer cell lines in vitro and in vivo and has been entered into a number of oncological trials. However, little is known about its mechanism(s) of action or its effects on normal cells such as fibroblasts. In this study, the effects of fenretinide on both epidermoid carcinoma cells of vulva (cell line A431) and normal human dermal fibroblasts, both as monolayers and also grown in 3D cell culture systems, have been investigated. The 3D cell culture system contained normal human fibroblasts embedded in a type I collagen gel with the carcinoma cells seeded on top of the collagen gel, which mimics the epidermoid carcinoma. Fenretinide significantly inhibited the rate of DNA synthesis of carcinoma cells, while there was little effect on fibroblasts on monolayers, at 10(-6)-10(-5) M, which are clinically attainable doses. Fenretinide at 5 x 10(-6) M induced apoptosis characterised by cell shrinkage, membrane blebbing, nuclear condensation and/or fragmentation, and cell detachment in carcinoma cells, but not fibroblasts from monolayers. Fenretinide also reduced the viability of carcinoma cells in the 3D cell culture system without affecting fibroblasts. These data show that fenretinide may preferentially induce apoptosis in epidermoid carcinoma cells.

Animals↗
PubMed2000

IUBMB updates Ph.D. standards.

The Education Committee of the International Union of Biochemistry (IUB, but IUBMB since 1991) published its report on "Standards for the Ph.D. Degree in Biochemistry and Molecular Biology" in 1989. Developments since then have led to the disappearance of the traditional demarcations between many of the biological disciplines, while information technology and bioinformatics have revolutionized the analysis, storage, and communication of scientific data. To meet these challenges, that report has now been revised through a broad interdisciplinary and international consultation. This has led to the recent publication, on behalf of the same Committee, of "Standards for the PhD Degree in the Molecular Biosciences". Like its predecessor this revised report not only defines in behavioural terms the qualities and skills expected of doctoral graduates by the international community of molecular bioscientists but also offers useful suggestions and advice as to how those skills can be developed and maximized. In addition, it discusses various topics related to doctoral education.

Biochemistry↗
PubMed1999

Fenretinide and its relation to cancer.

Retinoids, natural or synthetic substances which have vitamin A activity, have a well-known reputation for their antitumour and differention-inducing activity in vitro and in vivo. More than 1500 retinoids have been tested so far but very few of them have been entered into clinical trials because of their side-effects. All-trans-N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide) is a synthetic retinoid that is reported to have fewer side-effects compared to naturally occurring retinoids such as all-trans retinoic acid (ATRA) and 9-cis retinoic acid. In addition, fenretinide has been shown to induce cell death (apoptosis) even in ATRA-resistant cell lines. Although the mechanism by which fenretinide acts is not entirely known it is considered to be a promising drug and seems to induce apoptosis via different pathway(s) from classical retinoids. In this review, we discuss possible mechanisms of fenretinide action and summarize results of clinical trials.

Animals↗
PubMed1998

A matrix metalloproteinase inhibitor which prevents fibroblast-mediated collagen lattice contraction.

Matrix metalloproteinases (MMPs) and the specific tissue inhibitors of metalloproteinases (TIMPs) are involved in tissue turnover in normal and pathological processes including wound healing. Marimastat, a potent inhibitor of MMPs, was used to investigate the role of MMPs in an in vitro wound contraction model, the dermal equivalent, in which fibroblasts are grown in a collagen matrix. Marimastat inhibited fibroblast-mediated lattice contraction and this inhibition was reversible upon removal of the inhibitor, indicating that MMPs play an important role in fibroblast-mediated collagen lattice contraction, modelling what may happen when granulation tissue contracts in a healing wound.

Adult↗
PubMed1997

Integrin receptor involvement in actin cable formation in an in vitro model of events associated with wound contraction.

Actin cables have been reported to act in vivo as contractile 'purse strings' capable of closing embryonic wounds through generation of circumferential tension. Furthermore, their involvement in wounds within in vitro model systems suggests that actin cable contraction may be an important mechanism involved in the process of wound closure. The aim of this study therefore, was to investigate the appearance of actin cables in a contracting fibroblast populated collagen lattice, an in vitro model of events associated with wound contraction. Utilising this in vitro model, the time-course of actin cable production was investigated and the involvement of integrin receptors analysed using immunofluorescent labelling techniques. Over a period of hours distinct cellular cable-like structures developed at the edges of collagen lattices coinciding with the onset of contraction. Cellular organisation within the cable was evident as was polymerisation of actin microfilaments into elongated stress fibres forming a continuous cell-cell 'actin cable' around the circumference of the lattice. Immunolocalisation demonstrated that integrin receptor subunits beta 1 and alpha 2 but not alpha 5 were involved in apparent intimate cell-cell contact between juxtaposed fibroblasts within this actin cable. This study demonstrates the involvement of integrin receptors in actin cable formation within collagen lattice systems undergoing reorganisation. Such integrin involvement may enable participating cells to respond to the tensional status of their surrounding environment and via cell-cell communication, to permit a co-ordinated contraction of the cable. It is concluded that integrin receptor involvement in active actin cable contraction may be involved in the process of wound contraction.

Actins↗