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Biomedical subjects

S Murray

Publications and source records attributed to S Murray.

At least 37 records · Page 2Linked to original sources

X-ray photoelectron spectroscopy and magnetic studies on the effect of pore size, wall thickness, and wall composition on superparamagnetic cobaltocene mesoporous Nb, Ta, and Ti composites.

Recent results in our group demonstrated that mixed oxidation state mesoporous niobium oxide cobaltocene composites display superparamagnetism at certain composition ratios. This was the first report of superparamagnetism in nanoscale molecular ensembles. A series of mesoporous niobium oxide materials were synthesized in order to understand the role of pore size and thickness of the walls in the mesostructure on the magnetic properties. Mesoporous Ti oxide and Ta oxide composites were also synthesized in order to investigate the effect of changing the wall composition on the magnetic properties of this new series of materials. All samples were characterized by X-ray diffraction, nitrogen adsorption, ultraviolet spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and superconducting quantum interference device magnetometry. The results of this study showed that variation of wall thickness or pore size in the Nb system had little effect on the properties and that superparamagnetism most likely arises from mixed oxidation state cobaltocene grains residing in the individual pores and not from the free electrons in the mesostructure or much larger domains. The Langevin function was applied to the isothermal magnetic data from the Nb composites and gave mean superparamagnetic particle sizes of ca. 14 nm in each system. The Co(II) to Co(III) ratios in these materials were approximately 1:1. The Ti and Ta materials showed no sign of superparamagnetism and only very low levels of neutral cobaltocene in the pores. This suggests that a critical amount of cobaltocene is required to bring about superparamagnetic behavior.

Journal Article↗

Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor.

PURPOSE: Overexpression of the ErbB family of growth factor receptors is present in a wide variety of human tumors and is correlated with poor prognosis. The purpose of this study was to determine the effects of a novel small molecule ErbB tyrosine kinase inhibitor, CI-1033, in combination with ionizing radiation on breast cancer cell growth and survival. MATERIALS & METHODS: Growth assays were performed on ErbB-overexpressing human breast cancer cells developed in our laboratory in the presence of 0.1-1.0 microM CI-1033 (Parke Davis). Clonogenic survival assays were performed in the presence of ionizing radiation with or without CI-1033. For some experiments, clonogen numbers, defined as the product of surviving fraction and total number of cells, were calculated at each time point during a course of multifraction radiation. RESULTS: CI-1033 potently inhibited the growth of ErbB-overexpressing breast cancer cells. A single 48-h exposure of 1 microM CI-1033 resulted in growth inhibition for 7 days, whereas three times weekly administration resulted in sustained growth inhibition. Clonogenic survival was modestly decreased after a 7-day exposure to CI-1033. Exposure to both CI-1033 and radiation (6 Gy) yielded a 23-fold decrease in clonogenic survival compared to radiation alone. In a multifraction experiment, exposure to CI-1033 and three 5-Gy fractions of gamma radiation decreased the total number of clonogens in the population by 65-fold compared to radiation alone. CONCLUSION: CI-1033 results in potent growth inhibition and modest cytotoxicity of ErbB-overexpressing breast cancer cells, and has synergistic effects when combined with ionizing radiation. These data suggest that CI-1033 may have excellent clinical potential both alone and in combination with radiation therapy.

Breast Neoplasms↗

Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age.

Age effects on telomere length and telomerase expression in peripheral blood lymphocytes were analyzed from 121 normal individuals age newborn to 94 years and revealed several new findings. 1) Telomere shortening was observed in CD4+ and CD8+ T and B cells with age. However, the rate of telomere loss was significantly different in these populations, 35 +/- 8, 26 +/- 7, and 19 +/- 7 bp/year for CD4+ and CD8+ T and B cells, respectively. In addition, CD4+ T cells had the longest average telomeres at all ages, followed by B cells, with CD8+ T cell telomeres the shortest, suggesting that these lymphocyte populations may have different replicative histories in vivo. 2) Telomerase activity in freshly isolated T and B cells was indistinguishably low to undetectable at all ages but was markedly increased after Ag and costimulatory receptors mediated stimulation in vitro. Furthermore, age did not alter the magnitude of telomerase activity induced after stimulation of T or B lymphocytes through Ag and costimulatory receptors or in response to PMA plus ionomycin treatment. 3) The levels of telomerase activity induced by in vitro stimulation varied among individual donors but were highly correlated with the outcome of telomere length change in CD4+ T cells after Ag receptor-mediated activation. Together, these results indicate that rates of age-associated loss of telomere length in vivo in peripheral blood lymphocytes is specific to T and B cell subsets and that age does not significantly alter the capacity for telomerase induction in lymphocytes.

Adolescent↗

Induction of postnatal schwann cell death by the low-affinity neurotrophin receptor in vitro and after axotomy.

Schwann cells express the low-affinity neurotrophin receptor (p75), but no role for either the neurotrophins or their cognate receptors in Schwann cell development has been established. We have found that Schwann cells isolated from postnatal day 1 (P1) or P2 mice that were p75-deficient exhibited potentiated survival compared to wild-type cells after growth factor and serum withdrawal. There was, however, no disparity in the survival of p75-deficient and wild-type Schwann cells isolated at embryonic day 15, suggesting that the death-inducing effects of p75 are developmentally regulated. A comparable degree of cell death was also observed in the sciatic nerves of both wild-type and p75-deficient mice at P1. However, 24 hr after axotomy, there was a 13-fold increase in the percentage of apoptotic nuclei in the distal nerve stumps of the transected sciatic nerves of neonatal wild-type but not p75-deficient mice. The expression of both the p75 and nerve growth factor (NGF) genes was upregulated after axotomy in neonatal wild-type nerves. Collectively, these results suggest that NGF-mediated activation of p75 is likely to be an important mediator of Schwann cell apoptosis in the context of peripheral nerve injury.

Age Factors↗

Mass spectrometric detection and measurement of N2-(2'-deoxyguanosin-8-yl)PhIP adducts in DNA.

Capillary column gas chromatography-electron-capture mass spectrometry (GC-MS) and microbore liquid chromatography-positive ion electrospray mass spectrometry (LC-MS) have been used to measure the carcinogenic, food-derived, heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) adducted at C-8 of deoxyguanosine in DNA. For GC-MS analysis, PhIP was released from adducted DNA by alkaline hydrolysis and analysed as the di(3,5-bistrifluoromethylbenzyl) derivative, while for LC-MS analysis, the nucleoside N2-(2'-deoxyguanosin-8-yl)PhIP was generated by enzymic digestion of DNA and analysed intact. A deuterated analogue of N2-(2'-deoxyguanosin-8-yl)PhIP was used as an internal standard in both assays, which each had a limit of quantification of 200 pg/500 microg DNA. The two methods were used to analyse DNA extracted from h1A2v2 cells and HCT116 cells that had been exposed to PhIP.

Animals↗

Analysis of N(alpha)-methylhistamine by gas chromatography-mass spectrometry.

A gas chromatography-electron capture mass spectrometry assay has been developed for the histamine H3 receptor agonist, N(alpha)-methylhistamine (N(alpha)-MH). The assay is linear from 50 pg-10 ng, with a limit of detection of 50 pg/ml for gastric juice and plasma, and 50 pg/sample for bacteria (10(7)-10(8) CFU) and gastric tissue (5-10 mg wet weight). The limits of quantification are 100 pg/ml for gastric juice (%RSD=1.4) and plasma (%RSD=9.4), and 100 pg/sample for bacteria (%RSD=3.9) and tissue (%RSD=5.8). N(alpha)-MH was not present in human plasma, but low levels (1.4 ng/ml and 0.4 ng/ml) were detected in two samples of human gastric juice obtained from patients infected with Helicobacter pylori.

Gas Chromatography-Mass Spectrometry↗

Idiopathic hemorrhagic vasculopathy syndrome in seven black rhinoceros.

Idiopathic hemorrhagic vasculopathy syndrome (IHVS) was diagnosed in 7 black rhinoceros; this newly described syndrome is characterized by severe body swelling in conjunction with a rapid and profound decrease in Hct. The disorder may be acute or chronic, may recur, and is potentially fatal. Five of the rhinoceros survived an initial episode of IHVS, and 2 of these 5 survived a recurrent episode of IHVS. Two rhinoceros died during treatment of IHVS. Treatment protocols varied, but all 7 rhinoceros received broad-spectrum antibiotics, because an infectious cause was suspected. All rhinoceros also received nonsteroidal antiinflammatory drugs and supportive care. Idiopathic hemorrhagic vasculopathy syndrome has many similarities to other vasculopathies of domestic animals, such as equine purpura hemorrhagica, but it also appears to have unique identifying features. It has been hypothesized that IHVS may be an immune response to an as yet unidentified infectious agent. Thorough and extensive testing has not identified the potential causative agent, nor the factors that predispose some black rhinoceros to developing IHVS. Further research into the rhinoceros immune system is ongoing and should help elucidate the mechanisms through which IHVS develops.

Anemia↗

N alpha-methylhistamine: association with Helicobacter pylori infection in humans and effects on gastric acid secretion.

Infection with the bacterium Helicobacter pylori is associated with altered gastric acid secretion and gastrointestinal disease. Recent work has suggested that N alpha-methylhistamine, produced by the bacterium and acting on histamine receptors in gastric tissue, might be involved. Gastric juice and tissue biopsies from infected patients have been analysed for the presence of N alpha-methylhistamine using a specific and sensitive assay based on gas chromatography mass spectrometry. N alpha-Methylhistamine was detected in five of seven samples of gastric juice from infected patients (5-180 pmol/ml) but was absent in nine uninfected subjects. The compound was not found in fundic and antral biopsies from both subject groups. Helicobacter pylori, cultured on agar and in broth with and without added histamine, was found not to produce detectable levels of N alpha-methylhistamine. Instillation of this compound at 10(-5) mol/l into the gastric lumen produced a significant increase in acid secretion in vivo while plasma gastrin concentration remained unchanged. N alpha-Methylhistamine in gastric juice appears therefore to be associated with infection, although this product is not generated directly by the bacterium. The concentrations found are below those required to affect acid secretion or gastrin production in vivo, although higher local concentrations may exist around a site of infection.

Gas Chromatography-Mass Spectrometry↗

Laser ultrasonic surface wave inspection of alumina ceramics of varying density

In this paper, the surface acoustic wave velocity results acquired from the inspection of specially manufactured and characterised alumina ceramic materials are presented. Ultrasonic velocity data of alumina-based ceramics in the range 60-100% theoretical density was generated utilising non-contacting laser-ultrasonic measurements based on laser generation and detection of surface acoustic waves with the objective of creating a routine technique for industrial advanced alumina inspection. With linear fitting the surface acoustic wave velocity data serves as a calibration graph for using laser ultrasonics for routine monitoring of alumina. A second laser ultrasonic technique based on the laser generation and foil transducer detection of surface acoustic waves was used to validate the surface acoustic wave velocities measured by the laser generation/detection technique.

Journal Article↗

Amelioration of odorous components in spent mushroom compost.

Volatile sulfur compounds, as well as other volatiles found in the headspace above spent mushroom compost (SMC), were analyzed by gas chromatography and mass spectrometry. Data from these techniques as well as organoleptic evaluation of both the SMC and the chromatographic eluant indicated that the volatile sulfur compounds and cresol were important odorous components in SMC; cresol was reported as a musty, cattle-feces aroma. Samples consisted of headspaces from untreated SMC as well as SMC stirred with 1% (by weight) powered activated carbon (PAC). SMC stirred with and without PAC reduced headspace volatile concentrations, but the stirred with added PAC further decreased concentrations of important malodorants such as volatile sulfur compounds and cresol.

Agaricales↗

A randomised controlled trial of intravenous versus inhalational analgesia during outpatient oocyte recovery.

To compare the efficacy and acceptability of conventional intravenous sedation with patient-controlled inhalational isodesox, 57 women undergoing outpatient oocyte recovery were randomly allocated to receive isodesox by face mask, while 55 women were given intravenous fentanyl and midazolam. Women's satisfaction with pain relief, peroperative pain, clouding of memory and the surgeons' assessment of operating conditions were evaluated. Thirty-eight women in the inhalation group (67%) and 41 (75%) women in the intravenous group were 'very satisfied' with their analgesia (p = 0. 41). The mean (SD) pain score in women given isodesox was 46.8 (34. 7), while in the intravenous group it was 34.1 (21.3) (p = 0.02). Oxygen saturation levels < 94% were recorded in one woman using isodesox and in 16 (29%) women given intravenous analgesia. Despite higher pain scores, in comparison with the conventional analgesia, patient-controlled isodesox offers a safer method of pain relief with comparable satisfaction rates.

Administration, Inhalation↗

Diagnostic and therapeutic evaluation of an anti-Langerhans cell histiocytosis monoclonal antibody (NA1/34) in a new xenograft model.

Scintigraphy using monoclonal antibodies has been suggested as a possible adjunct to conventional staging techniques for the routine staging and diagnosis of Langerhans cell histiocytosis. In this study we have developed a model for Langerhans cell histiocytosis comprising a CD1a-positive subcutaneous xenograft in the flanks of nude (nu/nu) mice. The anti-CD1a murine monoclonal antibody NA1/34 was investigated for its potential both as an imaging and as a therapeutic targeting agent in this model. Biodistribution with NA1/34 compared with irrelevant isotype-matched monoclonal antibody demonstrated specific accumulation within the xenografts of 10.0%id per g (percentage injected dose per gram) and 3.3%id per g at 48 h postinjection, respectively. NA1/34 displayed no specific accumulation to CD1a-negative xenografts. F(ab')2 fragments of NA1/34 displayed a faster clearance time of 19.6 h compared with the intact antibody, 122.4 h, resulting in a more rapid maximum xenograft uptake time of 5 h compared with 48 h postinjection for the intact antibody. Although the overall xenograft/tissue ratio for the F(ab')2 was at no time greater than that for the intact antibody, the F(ab')2 did display dramatically greater xenograft/blood ratios, reaching 19:1 at 120 h postinjection Xenograft regression using single doses of 350 microCi and 500 microCi 131I-labeled NA1/34 significantly (p < 0.001) delayed xenograft progression compared with control nonirradiated xenografts, with average delays of 3.2 and 5.7 times the control, respectively. This study suggests that the anti-CD1a monoclonal antibody, NA1/34, offers advantages in the prognosis and staging of Langerhans cell histiocytosis, in a human setting. We discuss the advantages of radioimmunoscintigraphy over conventional differential diagnostic techniques. The potential for the future radioimmunotherapy of Langerhans cell histiocytosis is also discussed.

Animals↗

Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot.

BACKGROUND: Antibiotics are over-prescribed for respiratory tract infections in Australia. OBJECTIVES: The aim of this study was to describe the clinical predictors of GPs' prescribing of antibiotics. METHODS: We used Clinical Judgment Analysis to study the responses of GPs to hypothetical paper-based vignettes of a 20-year-old with a respiratory tract infection. The nature of four symptoms and signs (colour of nasal mucous discharge; soreness of the throat; presence of fever; and whether any cough was productive of sputum) was varied and their effect on prescribing measured using logistic regression. RESULTS: Twenty GPs participated. The nature of each symptom and sign significantly predicted prescribing of an antibiotic. Cough productive of yellow sputum; presence of sore throat; fever; and coloured nasal mucus increased the probability of an antibiotic being prescribed. CONCLUSIONS: GPs are influenced by clinical signs and symptoms to use antibiotics for respiratory infections for which there is poor evidence of efficacy from the literature.

Adult↗

Dietary soya beans and kidney beans stimulate secretion of cholecystokinin and pancreatic digestive enzymes in 400-day-old Hooded-Lister rats but only soya beans induce growth of the pancreas.

The effects of age on cholecystokinin (CCK) release, pancreatic enzyme secretion, and growth of the pancreas mediated by dietary kidney beans or soya beans were evaluated in trials with 30-, 90-, 250-, and 400-day-old rats. Soya beans increased blood CCK and caused hypersecretion of digestive enzymes and rapid pancreatic growth in all rats. Kidney beans also elevated circulating CCK and stimulated enzyme secretion. However, with 90-, 250-, and 400-day-old rats, the secretory responses were attenuated. Furthermore, kidney beans did not induce pancreatic growth in 250- and 400-day-old rats.

Aging↗

Variance and sample size calculations in quality-of-life--adjusted survival analysis (Q-TWiST).

The Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) statistic previously introduced by Glasziou, Simes and Gelber (1990, Statistics in Medicine 9, 1259-1276) combines toxicity, disease-free survival, and overall survival information in assessing the impact of treatments on the lives of patients. This methodology has received positive reviews from clinicians as intuitive and useful, but to date, the variance of this statistic has remained unspecified. We review aspects of the Q-TWiST method for analyzing clinical trial data, extend the method to accommodate multiple treatment arms, and provide closed-form asymptotic variance formulas. We also provide a framework for designing Q-TWiST clinical trials with sample sizes determined using the derived asymptotic variance formulas. Trials currently collecting quality of life data did not have the benefit of these sample size calculation techniques in designing their studies.

Biometry↗

Nonparametric rank-based methods for group sequential monitoring of paired censored survival data.

This research gives methods for nonparametric sequential monitoring of paired censored survival data in the two-sample problem using paired weighted log-rank statistics with adjustments for dependence in survival and censoring outcomes. The joint asymptotic closed-form distribution of these sequentially monitored statistics has a dependent increments structure. Simulations validating operating characteristics of the proposed methods highlight power and size consequences of ignoring even mildly correlated data. A motivating example is presented via the Early Treatment Diabetic Retinopathy Study.

Biometry↗

Chronic urticaria: a Canadian perspective on patterns and practical management strategies.

BACKGROUND: Chronic urticaria is a common condition and is a source of great frustration to patients. It has been suggested that there may be differences among physicians in their approach to this common clinical entity. OBJECTIVE AND METHOD: A questionnaire was distributed Canada-wide to allergists, dermatologists, and a selection of practitioners with an interest in alternative medicine. The survey included questions on demographics, epidemiology, causative factors, diagnostic methods, therapeutic strategies, follow-up advice, and efficacy of therapies, with emphasis on personal experience. RESULTS: The response rates of allergists and dermatologists were 31% and 36%, respectively. There was wide representation from all regions of Canada and from physicians from all age groups, both genders, different types of practice, and years in practice. The reported incidence per month was 13 and 4 patients for allergists and dermatologists, respectively. The prevalence was 199 and 44 patients by allergists and dermatologists, respectively. Comparison of causative factors showed differences in the experiences of the two groups. Diagnostic investigations were requested in a similar pattern with respect to timing. The specific tests ordered by the groups showing statistical difference were complete blood count (CBC), differential, C4 complement, antinuclear antibodies, and IgE antibody assay. Allergists chose the skin prick test (100%) as the most important allergy test. Dermatologists ranked skin prick (50%), radioallergosorbent test (RAST) (20%), and skin patch (30%) as the most important tests. The top six choices of pharmaceutical therapies chosen by the groups were similar, but in a slightly different order. The responders ranked their personal selection of antihistamines according to effectiveness. Hydroxyzine (Atarax) and cetirizine (Reactine, Allegra) were selected as first and second most effective agents by both groups. The results also show effective experience by both groups with nonsedating and sedating antihistamines. Also, doxepin, ketotifen, and cimetidine are used frequently by both groups. The experience of dermatologists in Canada with respect to other modalities including psoralen ultraviolet A (PUVA) therapy, danazol, chelation, calcium channel blockers, and acyclovir is limited and efficacy is ranked either neutral or ineffective. Allergists reported even less experience with these therapies. CONCLUSION: Allergists and dermatologists across Canada show interesting similarities and differences in their practical approach to the management of chronic urticaria. With the sharing of this information, these two specialties will be better equipped to effectively manage patients suffering from chronic urticaria.

Adult↗