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P A Burns

Publications and source records attributed to P A Burns.

At least 19 recordsLinked to original sources
PubMed2003

Angiogenesis mediated by metabolites is dependent on vascular endothelial growth factor (VEGF).

Metabolites released from hypoxic tissues have recently been reported to be angiogenic, although it remains to be clarified if they have a role independent of the upregulation of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF). In an attempt to conclusively evaluate their role, the metabolites lactate, pyruvate, malate and adenosine were tested in a two-dimensional in vitro angiogenesis assay which consists of human umbilical vein endothelial cells (HUVECs) co-cultured with fibroblasts of dermal origin. In addition, ethanol was tested. Metabolism of ethanol leads to increased levels of lactate and malate, which may explain its recently reported angiogenic properties. Lactate, malate, adenosine and ethanol produced a significant angiogenic response, although this was only observed at certain concentrations. However this angiogenic response was abolished when repeated in the presence of neutralising anti-VEGF antibodies. The results of this study therefore indicate that the angiogenic potential of metabolites is dependent upon increased expression of VEGF.

Endothelium, Vascular↗
PubMed2000

The yeast p53 functional assay: a new tool for molecular epidemiology. Hopes and facts.

The assumption of molecular epidemiology that carcinogens leave fingerprints has suggested that analysis of the frequency, type, and site of mutations in genes frequently altered in carcinogenesis may provide clues to the identification of the factors contributing to carcinogenesis. In this mini-review, we revise the development, and validation of the yeast-based p53 functional assay as a new tool for molecular epidemiology. We show that this assay has some very interesting virtues but also has some drawbacks. The yeast functional assay can be used to determine highly specific mutation fingerprints in the human p53 cDNA sequence. Discrimination is possible when comparing mutation spectra induced by sufficiently different mutagens. However, we also reported that the same carcinogen may induce distinguishable mutation spectra due to known influencing factors.

Alkylating Agents↗
PubMed2000

Health-promoting educational practices related to osteoporosis.

This descriptive study was conducted to determine what routine osteoporosis-related education was provided to women aged 49 years and younger and women aged 50 years and older. Forty-seven primary care providers (PCPs) including physicians/osteopaths (74%), nurse practitioners (19%), and physician assistants (7%) participated in the study. Significant differences were found in the frequency of performing osteoporosis risk assessments (t = 7.697, p = 0.0), performance of diet histories (t = 6.212, p = 0.0), exercise assessments (t = 2.483, p = 0.0), and provision of osteoporosis-related information (t = 8.700, p = 0.0) with women aged 50 or older receiving more attention than women aged 49 years or younger. Taken together, the findings of this study suggest that primary care providers generally assess the risk factors associated with osteoporosis and provide education more frequently to women 50 years of age and older. Despite the small sample size, there was a clear age-related difference in the assessment of osteoporosis risk factors and provision of risk-modifying education.

Age Factors↗
PubMed1999

5-methylcytosine at HpaII sites in p53 is not hypermutable after UVC irradiation.

Using a yeast based p53 functional assay we previously demonstrated that the UVC-induced p53 mutation spectrum appears to be indistinguishable from the one observed in Non Melanoma Skin Cancer (NMSC). However, position 742 (codon 248, CpG site) represented the major hot spot in NMSC but was not found mutated in the yeast system. In order to determine whether UVC-induced mutagenic events may be facilitated at methylated cytosine (5mC), a yeast expression vector harbouring a human wild-type p53 cDNA (pLS76) was methylated in vitro by HpaII methylase. Methylation induced 98% protection to HpaII endonuclease. Unmethylated and methylated pLS76 vectors were then UVC irradiated (lambda(max): 254 nm) and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. The results revealed that: (i) 5mC at HpaII sites did not cause any difference in the UVC-induced survival and/or mutagenicity; (ii) none of the 20 mutants derived from methylated pLS76 showed p53 mutations targeted at HpaII sites; (iii) the UVC-induced p53 mutation spectra derived from methylated and unmethylated pLS76 were indistinguishable not only when classes of mutations and hot spots were concerned, but also when compared through a rigorous statistical test to estimate their relatedness (P = 0.85); (iv) the presence of 5mC did not increase the formation of photo-lesions at codon 248, as determined by using a stop polymerase assay. Although based on a limited number of mutants, these results suggest that the mere presence of 5mC at position 742 does not cause a dramatic increase of its mutability after UVC irradiation. We propose that position 742 is a hot spot in NMSC either because of mutagenic events at 5mC caused by other UV components of solarlight and/or because not all the NMSC are directly correlated with UV mutagenesis but may have a "spontaneous" origin.

5-Methylcytosine↗
PubMed1999

Relationship between DNA methylation and mutational patterns induced by a sequence selective minor groove methylating agent.

Me-lex, a methyl sulfonate ester appended to a neutral N-methylpyrrolecarboxamide-based dipeptide, was synthesized to preferentially generate N3-methyladenine (3-MeA) adducts which are expected to be cytotoxic rather than mutagenic DNA lesions. In the present study, the sequence specificity for DNA alkylation by Me-lex was determined in the p53 cDNA through the conversion of the adducted sites into single strand breaks and sequencing gel analysis. In order to establish the mutagenic and lethal properties of Me-lex lesions, a yeast expression vector harboring the human wild-type p53 cDNA was treated in vitro with Me-lex, and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. The results showed that: 1) more than 99% of the lesions induced by Me-lex are 3-MeA; 2) the co-addition of distamycin quantitatively inhibited methylation at all minor groove sites; 3) Me-lex selectively methylated A's that are in, or immediately adjacent to, the lex equilibrium binding sites; 4) all but 6 of the 33 independent mutations were base pair substitutions, the majority of which (17/33; 52%) were AT-targeted; 5) AT --> TA transversions were the predominant mutations observed (13/33; 39%); 6) 13 out of 33 (39%) independent mutations involved a single lex-binding site encompassing positions A600-602 and 9 occurred at position 602 which is a real Me-lex mutation hotspot (n = 9, p < 10(-6), Poisson's normal distribution). A hypothetical model for the interpretation of mutational events at this site is proposed. The present work is the first report on mutational properties of Me-lex. Our results suggest that 3-MeA is not only a cytotoxic but also a premutagenic lesion which exerts this unexpected property in a strict sequence-dependent manner.

Adenine↗
PubMed1999

Molecular detection of tumour DNA in serum and peritoneal fluid from ovarian cancer patients.

We have analysed DNA extracted from the serum and peritoneal fluid of 20 ovarian cancer patients for the presence of tumour-specific genetic alterations. The 20 patients included six with stage Ia disease. Using six polymorphic microsatellite loci we were able to detect novel alleles or loss of heterozygosity in 17/20 serum samples and 12/19 peritoneal fluid samples. Tumour-specific abnormalities were detected in the serum of all but one of the stage Ia cases. Half of the occurrences of loss of heterozygosity identified in primary tumour material were detectable in the serum samples. Novel alleles indicative of microsatellite instability were found in 3/6 patients with stage Ia disease but in only 1/14 of patients with more advanced disease. One of the eight patients in the control group displayed abnormalities in her serum DNA. The ease with which tumour-specific alterations were detected in serum and peritoneal samples from ovarian cancer patients, using a panel of only six polymorphic microsatellite markers on four chromosomes, suggests that molecular detection methods could prove useful in the staging, monitoring and screening of this disease.

Alleles↗
PubMed1999

Continence for women: evidence-based practice.

Approximately 20% of women ages 25-64 years experience urinary incontinence. The symptoms increase during perimenopause, when 31% of women report that they experience incontinent episodes at least once per month. Bladder training and pelvic muscle exercise are the recommended initial treatment and can be taught effectively in the ambulatory care setting. Bladder training enables women to accommodate greater volumes of urine and extend between-voiding intervals. Pelvic muscle exercise increases muscle strength and reduces unwanted urine leakage. Accumulated research results provide evidence-based guidelines for nursing practice. The Association of Women's Health, Obstetric and Neonatal Nurses has identified continence for women as the focus of its third research utilization project. This article presents the rationale, evidence base, and educational strategies compiled by the Research Utilization 3 Nurse Scientist Team. Nurses can enable women to incorporate these noninvasive techniques into self-care.

Adult↗
PubMed1998

Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer.

Ultraviolet (UV) light has been associated with the development of human non-melanoma skin cancers (NMSC). Such cancers often exhibit mutations in the p53 tumour suppressor gene. In order to determine the UV-induced p53 mutation spectrum, a yeast expression vector that harbours a human wild-type p53 cDNA was UV-irradiated in vitro and transfected into a yeast strain that contained the ADE2 gene regulated by a p53-responsive promoter. Forty-five mutant clones contained 51 mutations. Seven mutations were tandem base pair substitutions, four of which being CC-->TT, hallmark mutations of UV mutagenesis. Eighty percent (41/51) of the mutations were single or non-tandem base pair substitutions, the majority of which (27/41) were C-->T transitions. Ninety-five percent of such mutations occurred at dipyrimidine sites. Through a rigorous statistical test, the UV-induced p53 mutation spectrum appears to differ significantly (P < 0.008) from the one induced by the antineoplastic drug chloroethyl-cyclohexyl-nitrosourea, and to be indistinguishable from the one observed in NMSC (P = 0.4). These results demonstrate that the assay allows the determination of carcinogen-specific p53 mutation fingerprints and represents a new tool for molecular epidemiology.

DNA, Complementary↗
PubMed1997

Effects of long-term maternal intravenous magnesium sulfate therapy on neonatal calcium metabolism and bone mineral content.

A prospective study was designed to determine whether calcium homeostasis and bone mineral content were affected adversely in preterm infants born to mothers receiving long-term antenatal therapy with magnesium sulfate. Preterm infants born to mothers receiving long-term antenatal therapy with magnesium sulfate and requiring prolonged bed rest for preterm labor were compared with infants of mothers not receiving magnesium sulfate but in whom prolonged bed rest was also required. Serum magnesium, calcium, phosphorus, osteocalcin, and parathyroid hormone were measured in infants at 0, 24, 48, and 72 h after delivery. Bone mineral content of the distal radius was measured 1 week postnatally and at term-equivalent postmenstrual age. Maternal serum mineral status indices obtained near delivery and bone indices were compared with those of their infants. The clinical characteristics and morbidities of the infants were similar between groups. We observed significantly greater serum concentrations of magnesium, phosphorus, and osteocalcin during the 72 h after delivery and a lower serum calcium concentration which normalized by 72 h in preterm infants whose mothers were treated with magnesium sulfate compared with infants whose mothers did not receive magnesium sulfate. Both groups, however, had similar radius bone mineral content measurements and anthropometric indices after delivery. These data suggest that although preterm infants born to mothers treated with magnesium sulfate have delayed clearance of magnesium and phosphorus, they have a normalization of serum calcium by 72 h after delivery and no significant differences in bone mineral content after delivery compared with infants whose mothers do not receive magnesium sulfate.

Adult↗
PubMed1997

A hot spot for p53 mutation in transitional cell carcinoma of the bladder: clues to the etiology of bladder cancer.

Twenty-eight transitional cell carcinomas of the bladder, grade 2 or 3, were analyzed for the presence of p53 mutations. Thirteen tumors were found to contain 14 mutations. These were all base substitution mutations, of which nine were GC-->AT transitions (three at CpG sites). The remaining five mutations were transversions (three GC-->CG, one GC-->TA, and one AT-->TA). Four of the mutations were found at codon 280. A comparison with other studies of bladder tumors reveals that a region encompassing codons 280 and 285 represents a hot spot for p53 mutation in bladder cancer. The 280/285 hot spot lies within two purine-rich sequences that may provide some clues to the identity of potential bladder carcinogens. A comparison of mutations from bladder tumors of smokers and nonsmokers reveals no significant differences.

Adult↗
PubMed1996

Molecular screening of multifocal transitional cell carcinoma of the bladder using p53 mutations as biomarkers.

Thirteen of 28 patients (46%) with grade 2-3 multifocal transitional cell carcinoma (TCC) of the bladder were found to have p53 mutations using DNA sequence analysis. These were subsequently utilized as tumor-specific biomarkers. Analysis of 17 episodes of recurrence from five of the patients revealed that all but one carried the identical mutation to the primary tumor. Thirty urine samples were collected, at initial diagnosis and during follow-up screening, from eight patients with mutations over a period of 24 months. Sequence analysis of PCR products generated from DNA extracted from the urine sediments was carried out. The p53 mutation seen in the primary tumors was detectable in 24 of 30 urine samples. The remaining six cases coincided with a negative cystoscopic examination. Interestingly, 6 of the 24 urine samples in which mutations were detectable also coincided with negative cystoscopy. The results are consistent with: (a) monoclonality of multifocal TCC; (b) the spread of TCC through a seeding mechanism; and (c) the long-term persistence of tumor cell clones (up to 97 months) within the bladder, even in the absence of obvious tumor growth.

Biomarkers↗
PubMed1995

Transgenic approaches to understanding the mechanisms of chemical carcinogenesis in mouse skin.

The use of animal models for human cancer has proved effective in the elucidation of those molecular events which are responsible for the various stages of tumour development. Chemical carcinogenesis in mouse skin has been studied as a model for human squamous cancer for several decades, and analysis of this model has led to the identification of a number of the changes which are involved in the evolution of malignancy. The use of transgenic and knockout mice offers a further avenue of advancement, allowing refinement of the model, and the ability to examine the consequences of individual events in vivo in greater detail. Additionally, crossing different transgenic or knockout animals represents a powerful tool to study the cumulative effects of several genetic alterations acting in concert.

Animals↗
PubMed1995

Limitations of R-average as an index of left ventricular isovolumic relaxation.

Freeman et al. (1993) have recently introduced a new index measuring isovolumic relaxation in the in situ left ventricle. This index, called the R-average, shows less variability than the traditionally used monoexponential time constant (tau), and could therefore represent an alternative measure of isovolumic relaxation during different physiological or pathophysiological interventions. However, the R-average represents the average pressure fall during isovolumic relaxation (isovolumic pressure fall divided by the isovolumic time period), and is therefore highly influenced by the end-systolic pressure level. The present study was done in order to assess whether small increments in loading conditions would alter the R-average without changes in the isovolumic relaxation period or the monoexponential pressure decay tau. We used a right heart bypass porcine model, and end-systolic pressure was altered between 92 and 140 mmHg by pre-loading (servo-pump) or after-loading (phenylephrine) in spontaneously beating and paced hearts. During loading, we found a significant increase in the R-average and a close correlation (r = 0.72 - 0.99) between R-average and en-systolic pressure. However, no alterations were found in the duration of the isovolumic relaxation time period or monoexponential pressure decay (tau) during these loading conditions. In our view, the R-average indicates the systolic loading level for the ventricle, but does not necessarily reflect alterations in the process of active relaxation.

Animals↗
PubMed1994

Determination of the ratios of 239Pu and 240Pu to 241Am for nuclear weapons test sites in Australia.

Recent measurements of the plutonium contamination at former nuclear weapons test sites in Australia have used the 59.5 keV gamma ray from the 241Am impurity to estimate levels of 239Pu and 240Pu. Measurements of the activity ratio of 239Pu to 241Am are presented for sites where suitable samples could be collected. Measurements of 240Pu were also made when interferences from fission products were absent. All measurements were made using a planar Ge detector of sufficient resolution to separate the 51.6 keV 239Pu gamma ray from the Ge K x-ray escape peaks and Compton scattering continuum from the much stronger 59.5 keV 241Am gamma ray. Results are given for most of the plutonium-contaminated sites in Australia.

Americium↗
PubMed1994

Significance and impact of urinary incontinence.

All nurses can play an important role in the detection of urinary incontinence (UI) in both community as well as institutional populations. With their advanced practice assessment and patient management skills, NPs are assuming a major role in the diagnosis and treatment of UI in primary and acute care settings, in home care, and in the management of chronic incontinence in long-term care. A strong commitment by the nursing community to emerge as a leading health care provider of incontinence assessment and management will be a major contribution to providing long awaited assistance for the 10 million incontinence sufferers in the United States. This article reviews the significance and impact of UI across all settings.

Adult↗