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Biomedical subjects

George Varigos

Publications and source records attributed to George Varigos.

9 recordsLinked to original sources
PubMed2006

Apoptosis may underlie the pathology of zinc-deficient skin.

The trace element zinc is essential for the survival and function of all cells. Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The effects of zinc deficiency are particularly obvious in the skin, seen as an erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals degenerative changes within keratinocytes. Despite the well-documented association between zinc deficiency and skin pathology, it is not clear which cellular processes are most sensitive to zinc deficiency and could account for the typical pathological features. We used the cultured HaCaT keratinocyte line to obtain insight into the cellular effects of zinc deficiency, as these cells show many characteristics of normal skin keratinocytes. Zinc deficiency was induced by growing cells in the presence of the zinc chelator, TPEN, or by growth in zinc-deficient medium. Growth of cells in zinc-deficient medium resulted in a 44% reduction of intracellular zinc levels and a 75% reduction in the activity of the zinc-dependent enzyme, 5'-nucleotidase, relative to the control cells. Over a period of 7 days of exposure to zinc-deficient conditions, no changes in cell viability and growth, or in the cytoskeletal and cell adhesion systems, were found in HaCaT cells. At 7 days, however, induction of apoptosis was indicated by the presence of DNA fragmentation and expression of active caspase-3 in cells. These results demonstrate that apoptosis is the earliest detectable cellular change induced by zinc deficiency in HaCaT keratinocytes. Our observations account for many of the features of zinc deficiency, including the presence of degenerate nuclei, chromatin aggregates and abnormal organization of keratin, that may represent the later stages of apoptosis. In summary, a major causal role for apoptosis in the pathology of zinc deficiency in the skin is proposed. This role is consistent with the previously unexplained diverse range of degenerative cellular changes seen at the ultrastructural level in zinc-deficient keratinocytes.

Apoptosis↗
PubMed2005

Unilateral acheiria and fatal primary pulmonary hypertension in a girl with incontinentia pigmenti.

We describe a newborn girl with incontinentia pigmenti (IP, MIM308300), unilateral acheiria, and fatal primary pulmonary hypertension. Limb deficiency has not been described previously in IP and pulmonary hypertension only on two previous occasions. A review of the cause of IP shows that these rare manifestations may not be unexpected, given the many roles of the underlying gene product.

Abnormalities, Multiple↗
PubMed2005

Eczema--practical management issues.

BACKGROUND: Eczema is a common, and at times challenging, condition to manage. It often involves an irritable child, concerned parents and numerous return visits. A variety of mainstream and alternative treatments can confuse both the clinician and patient. OBJECTIVE: This article aims to refresh readers by reviewing evidenced based treatment protocols, and exploring some of the new and evolving treatments in eczema. DISCUSSION: Managing eczema is a multifocal task involving a variety of medicinal and practical approaches. Education of parents and carers is critical. Having a clear plan that can be adapted to each patient's needs is helpful for all involved, with management focussing on control rather than cure. Simple emollients and preventive measures are used to reduce heat, dryness and prickling of the skin. Topical corticosteroids remain the gold standard in the treatment of the inflammation of eczema. However, combining topical steroids with the new calcineurin inhibitors, wet dressings and behavioural modification should increase the time interval between exacerbations.

Administration, Topical↗
PubMed2004

The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms.

Determining the roles of Rel/NF-kappaB transcription factors in mouse skin development with loss-of-function mutants has been limited by redundancy among these proteins and by embryonic lethality associated with the absence of RelA. Using mice lacking RelA and c-rel, which survive throughout embryogenesis on a tumor necrosis factor alpha (TNF-alpha)-deficient background (rela(-/-) c-rel(-/-) tnfalpha(-/-)), we show that c-rel and RelA are required for normal epidermal development. Although mutant fetuses fail to form tylotrich hair and have a thinner epidermis, mutant keratinocyte progenitors undergo terminal differentiation to form an outer cornified layer. Mutant basal keratinocytes are abnormally small, exhibit a delay in G(1) progression, and fail to form keratinocyte colonies in culture. In contrast to the reduced proliferation of mutant keratinocytes during embryogenesis, skin grafting experiments revealed that the mutant epidermis develops a TNF-alpha-dependent hyperproliferative condition. Collectively, our findings indicate that RelA and c-rel control the development of the epidermis and associated appendages during embryogenesis and regulate epidermal homeostasis in a postnatal environment through the suppression of innate immune-mediated inflammation.

Age Factors↗
PubMed2004

Fresh and cultured buccal cells as a source of mRNA and protein for molecular analysis.

We developed a method for obtaining viable buccal cells from mouthwash samples for use as a source of mRNA and protein. Immunofluorescent analysis showed that most cells were derived from nonkeratinized parabasal epithelia, with a minor proportion of proliferative cells. Gene expression was detected in buccal cells using reverse transcription PCR, Western blot analysis, and immunofluorescence. Using a keratinocyte-specific medium, buccal cells could be cultured on Matrigel-coated permeable filters for up to 2 weeks while maintaining the expression of some epithelial-specific markers, including cytokeratin 13, cytokeratin 10, transferrin receptor, and beta-integrin. The basal marker cytokeratin 14 and Ki67, an indicator of cellular proliferation, were detected in a few cells. We show that buccal cells can be obtained from a noninvasive procedure for use as a source of material for biochemical analyses. A population of the buccal cells can be maintained in culture for up to 2 weeks using keratinocyte-specific medium in combination with extracellular matrix.

Cell Culture Techniques↗
PubMed2003

Analysis of zinc transporter, hZnT4 ( Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk.

Zinc deficiency, causing impaired growth and development, may have a nutritional or genetic basis. We investigated two cases of inherited zinc deficiency found in breast-fed neonates, caused by low levels of zinc in the maternal milk. This condition is different from acrodermatitis enteropathica but has similarities to the "lethal milk" mouse, where low levels of zinc in the milk of lactating dams leads to zinc deficiency in pups. The mouse disorder has been attributed to a defect in the ZnT4 gene. Little is known about the expression of the human orthologue, hZnT4 (Slc30A4). Sequence analysis of cDNA, real-time PCR and Western blot analysis of hZnT4, carried out on control cells and cells from unrelated mothers of two infants with zinc deficiency, showed no differences. The hZnT4 gene was highly expressed in mouthwash buccal cells compared with lymphoblasts and fibroblasts. The hZnT4 protein did not co-localise with intracellular free zinc pools, suggesting that hZnT4 is not involved in transport of zinc into vesicles destined for secretion into milk. This observation, combined with phenotypic differences between the "lethal milk" mouse and the human disorder, suggests that the "lethal milk" mouse is not the corresponding model for the human zinc deficiency condition.

Adult↗
PubMed2003

Topical diclofenac in hyaluronan gel for the treatment of solar keratoses.

This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of a topical gel containing 3% diclofenac in 2.5% hyaluronan in 150 patients with solar keratoses (SK). The active treatment was compared with the vehicle only, hyaluronan gel, as placebo over a 12-week period. Patients in both groups applied the active treatment or placebo to a targeted area of skin (0.25 g b.d.). At 12 weeks the mean lesion-count reduction in the targeted area was not significantly different between treatments. However, at post-termination follow up (16 weeks), there was a highly significant decrease in the number of lesions, 6.2 +/- 7.5 standard deviations (SD) (56.1% reduction) in the active treatment group compared with 2.4 +/- 4.3 SD (23.6% reduction) in the placebo group (P < 0.001). Other efficacy measures (complete lesion resolution, >50% lesion reduction) were also significantly different (P < 0.01) between treatments at 16 weeks. In conclusion, topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated in this study, suggesting a role for this therapy in the treatment of SK.

Administration, Cutaneous↗
PubMedDate not supplied

Epidemiology and impact of childhood molluscum contagiosum: a case series and critical review of the literature.

Parents of 30 children with clinically diagnosed molluscum contagiosum were surveyed to assess their perception of the condition, its treatment, its impact on their everyday lives, and on the children themselves. Among parents, 82% reported that molluscum contagiosum concerned them moderately or greatly. Concerns focused on physical issues associated with the infection, such as scarring, itching, chance of spread to peers, pain, and the effects of treatments. Quality of life was not affected. Molluscum contagiosum was most common among school-age children. Eighteen of 29 respondents swam in public pools, a common activity in children of this age. All epidemiologic studies of molluscum contagiosum in otherwise healthy individuals, published since 1966, have been critically reviewed herein. The review confirms an association between swimming pool use and molluscum contagiosum. Age, living in close proximity, skin-to-skin contact, sharing of fomites, and residence in tropical climates were also associated with higher rates of infection while sex, seasonality, and hygiene showed no such association.

Attitude to Health↗