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Biomedical subjects

D Harris

Publications and source records attributed to D Harris.

At least 19 recordsLinked to original sources
PubMed2007

Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers.

Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered.

Australia↗
PubMed2006

Observation of muon neutrino disappearance with the MINOS detectors in the NuMI neutrino beam.

This Letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rates and energy spectra of charged current nu(mu) interactions are compared in two detectors located along the beam axis at distances of 1 and 735 km. With 1.27 x 10(20) 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336+/-14 events. The data are consistent with nu(mu) disappearance via oscillations with |Delta(m)2/32|=2.74 +0.44/-0.26 x10(-3)eV(2) and sin(2)(2theta(23))>0.87 (68% C.L.).

Journal Article↗
PubMed2006

Quality of life in a clinical sample of obese children.

OBJECTIVES: To measure health-related quality of life (HRQoL) in a clinical sample of obese children by child self-report and parent-proxy report; to compare quality of life assessments provided by obese children and their parents; to assess differences in quality of life between the obese clinical sample and healthy control children. DESIGN: Pairwise comparison of obese children matched for age, gender and socio-economic status with non-obese controls. SUBJECTS: One hundred and twenty-six obese children (body mass index (BMI) >/=98th centile) and 71 lean control children (BMI <85th centile). Controls were matched with 71 children from the obese clinical group (mean age 8.6, standard deviation (s.d.) 1.9 years; 33 M/38 F). MEASUREMENT: The Paediatric Quality of Life Inventory (UK) version 4 was self-administered to parents and to children aged 8-12 years and interview was administered to children aged 5-7 years. This questionnaire assessed physical, social, emotional and school functioning from which total, physical and psychosocial health summary scores were derived. RESULTS: In the obese clinical group (n=126), parent proxy-reported quality of life was low for all domains. In the obese clinical group, parent-reported scores were significantly lower than child self-reported scores in all domains except physical health and school functioning. Parent-proxy reports were significantly higher for healthy controls than obese children in all domains (median total score 85.2 vs 64.7; 95% confidence interval (CI) 15.6, 24.1). For child self-reports, only physical health was significantly higher for healthy controls than obese children (median score 81.3 vs 75.0; 95% CI 3.1, 12.5). CONCLUSIONS: HRQoL is impaired in clinical samples of obese children compared to lean children, but the degree of impairment is likely to be greatest when assessed using the parent perspective rather than the child perspective.

Body Mass Index↗
PubMed2006

Factitious buccal lesion secondary to bruxism in a child with cerebral palsy.

Children with cerebral palsy are at greater risk of a whole range of oral conditions than their peers. These include bruxism (tooth grinding), oral skill dysfunction, gross malocclusion due to effects of the abnormal orofacial muscle tone on tooth eruption, drooling of saliva, and poor oral hygiene. A challenging case of a painful buccal lesion in a 2 year old girl with cerebral palsy (CP) that did not respond to antifungal, antiviral or antibiotic treatment is presented as a factitious lesion. The recognition and significance of self-injurious behaviour and factitious lesions in children are discussed.

Bruxism↗
PubMed2005

Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention.

Zidovudine (AZT) lowers the perinatal transmission of HIV but can impair mitochondrial function by depleting mitochondrial DNA (mtDNA). AZT therapy and perinatal nutritional deprivation affect the body fat distribution, which influences glucose tolerance. We sought to model intrauterine exposure to AZT in humans to determine whether it interacts with low-protein diet (LPD) to impact on birth weight and glucose homeostasis in the offspring. Pregnant dams and their offspring were given AZT, an LPD, or AZT and an LPD (LPD + AZT). AZT reduced mtDNA copy number in liver and birth weight in the offspring and increased their fasting glucose and insulin (P = 0.021, 0.03, 0.001, and 0.011 respectively) at 6-8 wk of age. LPD decreased litter size and birth weight (P = 0.01 and 0.012). In the LPD + AZT group, birth weight and litter size were reduced compared with untreated controls, and fasting blood glucose and insulin were raised. There was a significant interaction between LPD and AZT on fasting insulin levels (P = 0.025). Islet size was not significantly affected, but the mean beta-cell area/islet was reduced in the LPD + AZT group compared with controls (P < 0.05). Early exposure to AZT interacts with LPD to impair fetal development in this model. This combination appeared to impair the supply of insulin and, hence, glucose homeostasis, perhaps as a result of impaired mitochondrial function. Although it is not certain that this can be extrapolated to humans, maternal nutritional deprivation combined with AIDS therapy could influence both birth weight and onset of diabetes.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells.

Multiple myeloma (MM) accounts for 1 % of all cancer deaths. Although treated aggressively, almost all myelomas eventually recur and become resistant to treatment. Atiprimod (2-(3-Diethylaminopropyl)-8,8-dipropyl-2-azaspiro[4,5] decane dimaleate) has exerted anti-inflammatory activities and inhibited oeteoclast-induced bone resorption in animal models and been well tolerated in patients with rheumatoid arthritis in phase I clinical trials. Therefore, we investigated its activity in MM cells and its mechanism of action. We found that Atiprimod inhibited proliferation of the myeloma cell lines U266-B1, OCI-MY5, MM-1, and MM-1R in a time- and dose-dependent manner. Atiprimod blocked U266-B1 myeloma cells in the G(0)/G(1) phase, preventing cell cycle progression. Furthermore, Atiprimod inhibited signal transducer and activator of transcription (STAT) 3 activation, blocking the signalling pathway of interleukin-6, which contributes to myeloma cell proliferation and survival, and downregulated the antiapoptotic proteins Bcl-2, Bcl-X(L), and Mcl-1. Incubation of U266-B1 myeloma cells with Atiprimod induced apoptosis through the activation of caspase 3 and subsequent cleavage of the DNA repair enzyme poly(adenosine diphosphate-ribose) polymerase. Finally, Atiprimod suppressed myeloma colony-forming cell proliferation in fresh marrow cells from five patients with newly diagnosed MM in a dose-dependent fashion. These data suggest that Atiprimod has a role in future therapies for MM.

Apoptosis↗
PubMed2005

Butane encephalopathy.

Volatile solvent abuse (VSA) is defined at the "intentional inhalation of a volatile substance for the purpose of achieving a euphoric state". The lifetime prevalence of VSA in the UK remains steady at around 15%, the fourth highest rate in Europe, and VSA is the most common form of drug abuse in the 11-15 year age group in England and Wales. A 13 year old girl presented to the accident and emergency unit following inhalation of butane based deodorant, which resulted in a prolonged semiconscious state with encephalopathic symptoms.

Adolescent↗
PubMed2005

In situ DMSO hydration measurements of HTS compound libraries.

Compounds used in high throughput screening (HTS) are typically dissolved in DMSO. These solutions are stored automation-friendly racks of wells or tubes. DMSO is hygroscopic and quickly absorbs water from the atmosphere. When present in DMSO compound solutions, water can accelerate degradation and precipitation. Understanding DMSO hydration in an HTS compound library can improve storage and screening methods by managing the impact of water on compound stability. A non-destructive, acoustic method compatible with HTS has been developed to measure water content in DMSO solutions. Performance of this acoustic method was compared with an optical technique and found to be in good agreement. The accuracy and precision of acoustic measurements was shown to be under 3% over the tested range of DMSO solutions (0% to 35% water by volume) and insensitive to the presence of HTS compounds at typical storage concentrations. Time course studies of hydration for wells in 384-well and 1536-well microplates were performed. Well geometry, fluid volume, well position and atmospheric conditions were all factors in hydration rate. High rates of hydration were seen in lower-volume fills, higher-density multi-well plates and when there was a large differential between the humidity of the lab and the water content of the DMSO. For example, a 1536-well microplate filled with 2microL of 100% DMSO exposed for one hour to a laboratory environment with approximately 40% relative humidity will absorb over 6% water by volume. Understanding DMSO hydration rates as well as the ability to reverse library hydration are important steps towards managing stability and availability of compound libraries.

Acoustics↗
PubMed2003

Five-year results of a new total replacement prosthesis for the finger metacarpo-phalangeal joints.

An unconstrained surface metacarpophalangeal joint replacement was developed with metal metacarpal and polyethylene phalangeal components, fixed by uncemented finned polyethylene plugs which allowed some metacarpal component motion. Clinical and radiological results in 13 joints in eight patients are presented after 5 years. One infection required revision at 3 months. There were no further complications. At final review there were no implant failures. Two of 13 joints showed lucency around the phalangeal component and one showed 2mm subsidence of the metacarpal component. No other adverse radiological features were observed. Seven patients had no pain and one had minor discomfort. Joint movement had improved from an arc of 27 degrees to 60 degrees and disability, assessed using the P.E.M. questionnaire, had improved from 77% to 9%.

Aged↗
PubMed2003

Eosinophils in a tri-cell multicellular tumor spheroid (MTS)/endothelium complex.

Eosinophils have been found in infiltrates of many different cancers. It is still unclear as to whether they are passive bystanders in the cellular milieu or active cellular agents in host responses. Thus their harmful or helpful nature remains equivocal. We have developed an in vitro tri-cell model of eosinophils, MCF-7 breast tumor cell spheroids and HUVEC endothelial cells to examine the binding and association of eosinophils with both the tumor and the endothelia and the ensuing action of the tumor. Eosinophils bound very rapidly to the tumor spheroid and remained tightly bound throughout the 24 hr culture period. Histological staining of the tri-cell complex revealed highly granulated eosinophils as well as large amounts of degranulated protein diffused throughout the spheroid. IL-5 treatment of eosinophil: MTS complexes resulted in destruction of the tumor cells, particularly those which had grown out from the spheroid onto the endothelial cells. Eosinophils, pretreated with IL-5 before interaction with the tumor or endothelial cells, bound aggressively to the endothelial cells, thereby preventing tumor attachment. This eosinophil tri-cell tumor model system mimics clinical observations with regards to binding to epithelial and endothelial cells, dispersal of granular proteins throughout the tumor and also tumor destruction. Because it closely mirrors in vivo cellular interactions, it allows one to study more closely the mechanism(s) of eosinophil killing, the modulation of eosinophil activity and the testing of therapeutic interventions. The accommodation of the model to tumor invasion, using metastatic tumor cells and extracellular matrices such as matrigel, will help to elucidate a role for eosinophils (and their mediators) in cancer invasion and metastasis.

Breast Neoplasms↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed2002

Recovery of zeta-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer.

Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent zeta-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including zeta-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for zeta-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower zeta-chain expression in circulating CD3(+) cells and a higher percentage of zeta-chain negative CD3(+) and CD4(+) cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of zeta-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer.

Aged↗
PubMed2002

High-speed plasmid isolation using 96-well, size-exclusion filter plates.

The accelerating pace of genomics analysis has necessitated the abbreviation of DNA sample preparation protocols. We have developed a size-exclusion-based system for the rapid isolation ofplasmid DNA in a 96-well microplate format. This high-speed protocol employs a modified alkaline lysis methodfor the preparation of the bacterial lysate, followed by three short vacuum filtration steps. Unlike traditional bind/wash/elute methods, there is no need to use chaotropic salts or ethanol. The samples are recovered from the top side of the MultiScreen96 PLASMID plates. Starting with bacterial cell pellets, the entire prycedure for purifying the plasmid DNA can be performed in 30 min with a multichannel pipettor. The high yields, reproducibility, and quality of the plasmids make this system a good choice for any cloning or DNA sequencing operation.

Base Sequence↗