Biomedical subjects

Peter G Parsons

Publications and source records attributed to Peter G Parsons.

25 records · Page 2Linked to original sources

PubMed2004

What is transforming growth factor-beta (TGF-beta)?

The TGF-beta superfamily of proteins produces a wide range of frequently opposing effects in different cells and tissues in the body. However, its activation and mode of action are only partially understood because of its complexity in structure and functions and the variability in its downstream targets. Current work on these cytokines focuses on their receptors and the intercellular signalling pathways, comparing bioactivities between cell types and tracking their physiological and immunological effects in vivo. Future research will yield important therapeutic applications and the ability to manipulate these proteins in vivo.

Animals↗

PubMed2004

Molecular introduction to head and neck cancer (HNSCC) carcinogenesis.

Of all human cancers, HNSCC is the most distressing affecting pain, disfigurement, speech and the basic survival functions of breathing and swallowing. Mortality rates have not significantly changed in the last 40 years despite advances in radiotherapy and surgical treatment. Molecular markers are currently being identified that can determine prognosis preoperatively by routine tumour biopsy leading to improved management of HNSCC patients. The approach could help decide which early stage patient should have adjuvant neck dissection and radiotherapy, and whether later stage patients with operable lesions would benefit from resection and reconstructive surgery or adopt a conservative approach to patients with poor prognosis regardless of treatment. In the future, understanding these basic genetic changes in HNSCC would be important for the management of HNSCC.

Apoptosis↗

PubMed2003

Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes.

Ageing results in a progressive, intrinsic and generalised imbalance of the control of regulatory systems. A key manifestation of this complex biological process includes the attenuation of the universal stress response. Here we provide the first global assessment of the ageing process as it affects the heat shock response, utilising human peripheral lymphocytes and cDNA microarray analysis. The genomic approach employed in our preliminary study was supplemented with a proteomic approach. In addition, the current study correlates the in vivo total antioxidant status with the age-related differential gene expression as well as the translational kinetics of heat shock proteins (hsps). Most of the genes encoding stress response proteins on the 4224 element microarray used in this study were significantly elevated after heat shock treatment of lymphocytes obtained from both young and old individuals albeit to a greater extent in the young. Cell signaling and signal transduction genes as well as some oxidoreductases showed varied response. Results from translational kinetics of induction of major hsps, from 0 to 24 h recovery period were broadly consistent with the differential expression of HSC 70 and HSP 40 genes. Total antioxidant levels in plasma from old individuals were found to be significantly lower by comparison with young, in agreement with the widely acknowledged role of oxidant homeostasis in the ageing process.

Adult↗

PubMed2003

A rapid method for determining recent sunscreen use in field studies.

The role of sunscreens in preventing skin cancer and melanoma is the focus of ongoing research. Currently, there is no objective measure which can be used in field studies to determine whether a person has applied sunscreen to their skin, and researchers must use indirect assessments such as questionnaires. We sought to develop a rapid, non-invasive method for identifying sunscreen on the skin for use in epidemiological studies. Our basic method is to swab the skin, elute any residues which have been adsorbed onto the swab by rinsing in ethanol, and submit the eluted washings for spectrophotometric analysis. In a controlled study, we applied 0.1 ml of sunscreen to a 50 cm(2) grid on both forearms of 21 volunteers. Each forearm was allocated one of 10 different sunscreen brands. The skin was swabbed after intervals of 20 min, 1 h, 2 h and 4 h. In a field study conducted among 12 children aged 2-4 years attending a child care centre, sunscreen was applied to the faces of half the children. Swabs were then taken from the face and back of all children without knowledge of sunscreen status. In the controlled study, sunscreen was clearly detectable up to 2 h after application for all brands containing organic sunscreen, and marginally detectable at 4 h. In the field study, this method correctly identified all children with and without sunscreen. We conclude that spectrophotometric analysis of skin swabs can reliably detect the presence of sunscreen on the skin for up to 2 h after application.

Adult↗

PubMed2003

Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: pigmentation marker, ultrastructural and UV-survival studies.

Recent population studies have demonstrated an association with the red-hair and fair-skin phenotype with variant alleles of the melanocortin-1 receptor (MC1R) which result in amino acid substitutions within the coding region leading to an altered receptor activity. In particular, Arg151Cys, Arg160Trp and Asp294His were the most commonly associated variants seen in the south-east Queensland population with at least one of these alleles found in 93% of those with red hair. In order to study the individual effects of these variants on melanocyte biology and melanocytic pigmentation, we established a series of human melanocyte strains genotyped for the MC1R receptor which included wild-type consensus, variant heterozygotes, compound heterozygotes and homozygotes for Arg151Cys, Arg160Trp, Val60Leu and Val92Met alleles. These strains ranged from darkly pigmented to amelanotic, with all strains of consensus sequence having dark pigmentation. UV sensitivity was found not to be associated with either MC1R genotype or the level of pigmentation with a range of sensitivities seen across all genotypes. Ultrastructural analysis demonstrated that while consensus strains contained stage IV melanosomes in their terminal dendrites, Arg151Cys and Arg160Trp homozygote strains contained only stage II melanosomes. This was despite being able to show expression of tyrosinase and tyrosinase-related protein-1 markers, although at reduced levels and an ability to convert exogenous 3,4-dihydroxyphenyl-alanine (DOPA) to melanin in these strains.

Alleles↗

PubMed2003

Induction of metallothionein in human skin by routine exposure to sunlight: evidence for a systemic response and enhanced induction at certain body sites.

Expression of metallothionein, an antioxidant induced by a variety of stimuli including ultraviolet light, was quantitated by immunohistochemistry in the skin of males aged over 50 who had known short- and long-term exposures to sunlight. Skin punch biopsies were taken from two sites in each subject: the hand in all subjects and a range of other sites matched to patients with a previously excised primary melanoma. Metallothionein expression (strongest in the basal layers of the epidermis and primarily nuclear) was associated with both short- and long-term exposure to sunlight. A plateau of staining intensity was reached after 3 h sun exposure, within the previous 3 d before biopsy. Expression was also elevated in the nonexposed skin sites of subjects who had recent sun exposure, indicating a systemic response to exposure of remote sites. Using the skin of the hand to normalize responses to chronic exposure between individuals, the systemically modulated response to sunlight was significantly greater on the unexposed back than on other sites. The possibility of ultraviolet-induced cytokines selectively modifying the response of skin on a site-specific basis was investigated. The circulating leukocytes, but not lymphocytes, of two individuals exposed to 1 minimal erythema dose whole-body solar-simulated ultraviolet showed increased interleukin-6 mRNA 4 h after exposure. Interleukin-6 was not directly induced in these cell populations 4 h after ultraviolet A or ultraviolet B irradiation ex vivo. Leukocytes may therefore contribute to and amplify the systemic effects of ultraviolet-induced interleukin-6 and metallothionein expression.

Gene Expression Regulation↗

PubMed2002

A histone deacetylase inhibitor, azelaic bishydroxamic acid, shows cytotoxicity on Epstein-Barr virus transformed B-cell lines: a potential therapy for posttransplant lymphoproliferative disease.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD), driven by the presence of Epstein-Barr virus (EBV), is becoming an increasingly important clinical problem after solid organ transplantation. The use of immunosuppressive therapy leads to the inhibition of the cytotoxic T cells that normally control the EBV latently infected B cells. The prognosis for many patients with PTLD is poor, and the optimal treatment strategy is not well defined. METHOD: This study investigates the use of a histone deacetylase inhibitor, azelaic bishydroxamic acid (ABHA), for its ability to effectively kill EBV-transformed lymphoblastoid cell lines. RESULTS: In vitro treatment of lymphoblastoid cell lines with ABHA showed that they were effectively killed by low doses of the drug (ID50 2-5 microg/ml) within 48 hr. As well as being effective against polyclonal B-cell lines, ABHA was also shown to be toxic to seven of eight clonal Burkitt's lymphoma cell lines, indicating that the drug may also be useful in the treatment of late-occurring clonal PTLD. In addition, ABHA treatment did not induce EBV replication or affect EBV latent gene expression. CONCLUSION: These studies suggest that ABHA effectively kills both polyclonal and clonal B-cell lines and has potential in the treatment of PTLD.

B-Lymphocytes↗