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Biomedical subjects

D Phillips

Publications and source records attributed to D Phillips.

At least 109 records · Page 6Linked to original sources
PubMed1995

Prognostic value of DNA ploidy as assessed with flow cytometry in uveal melanoma.

OBJECTIVE: To investigate the prognostic value of tumour cell DNA content, as determined with flow cytometry, in formalin-fixed paraffin-embedded tissue from patients with uveal melanoma. DESIGN: Case series. SETTING: Pathology Laboratory, Vancouver General Hospital. PATIENTS: Ninety patients with primary uveal (choroid) malignant melanoma diagnosed between 1975 and 1984 followed for at least 60 months. OUTCOME MEASURES: Tumour cell DNA content, 5-year and 10-year disease-specific survival rates. RESULTS: The DNA histograms were classifiable as diploid (67 cases) or aneuploid (18 cases) in 85 cases. On univariate analysis DNA content, age at diagnosis, histologic type of tumour, largest single tumour dimension and tumour volume were predictors of 10-year survival. Multivariate analysis with the stepwise Cox proportional hazards regression model did not confirm cellular DNA content as an independent prognostic factor. However, age at diagnosis, largest tumour dimension and presence of spindle vs. mixed or epithelioid cell pattern were significant predictors of death from uveal melanoma. CONCLUSIONS: DNA ploidy of uveal melanoma is not a statistically significant predictor of survival.

Adult↗
PubMed1994

beta-Carotene quenches singlet oxygen formed by isolated photosystem II reaction centers.

By measuring time-resolved luminescence emission at 1270 nm, we have detected singlet oxygen formation by illuminated, reaction centers of photosystem II isolated from Pisum sativum, which is in agreement with earlier work (Macpherson, A. N., Telfer, A., Barber, J., & Truscott, T. G. (1993) Biochim. Biophys. Acta 1143, 301-309). In this paper we show that the yield of singlet oxygen is significantly increased if the number of beta-carotene molecules bound per isolated complex is reduced from two to one. We conclude, therefore, that beta-carotene can act as an effective quencher of singlet oxygen in the photosystem II reaction center. This conclusion is supported by the finding that the rate of light-induced irreversible bleaching of chlorins in the reaction center is increased with decreasing beta-carotene levels. The results demonstrate the direct intermediacy of singlet oxygen in causing photooxidative damage within a biological environment and are discussed, specifically, in terms of the role of beta-carotene in protecting photosystem II against photoinhibition.

Carotenoids↗
PubMed1994

Isolated photosynthetic reaction center of photosystem II as a sensitizer for the formation of singlet oxygen. Detection and quantum yield determination using a chemical trapping technique.

Singlet oxygen formation by photosystem II reaction centers isolated from Pisum sativum has been detected by two chemical trapping techniques: histidine-dependent oxygen uptake and bleaching of p-nitrosodimethyl-aniline by the intermediary endoperoxide of histidine. The quantum yield of singlet oxygen formation determined by these methods was estimated to be 0.16 by comparison with the known quantum yields of standard singlet oxygen sensitizers. Singlet oxygen was formed on illumination of reaction centers under conditions that lead to formation of the triplet state of the primary electron donor, P680. Experiments with deuterated buffer and active oxygen scavengers indicated that singlet oxygen was the only active oxygen species produced by this reaction. Neither azide nor histidine, which are scavengers of singlet oxygen, protected against photobleaching of the chlorophyll of reaction centers that occurs concomitantly with singlet oxygen formation, suggesting that bleaching involves singlet oxygen generated within the protein matrix of the complex. Singlet oxygen sensitized exogenously by rose bengal (when excited specifically at 550 nm) was also found to bleach reaction center chlorophyll in a manner similar to the intrinsic mechanism. We conclude that singlet oxygen formed within the hydrophobic interior of the reaction center attacks the chlorophylls of P680, and presumably also amino acids in the vicinity, and that only the singlet oxygen that escapes to the medium is affected by added scavengers or deuterated medium. These experiments extend our earlier report of the detection of singlet oxygen by its luminescence at 1270 nm when isolated photosystem II reaction centers are illuminated (Macpherson, A. N., Telfer, A., Barber, J., and Truscott, T. G. (1993) Biochim. Biophys. Acta 1143, 301-309). Moreover, our results support the hypothesis that production of singlet oxygen underlies the vulnerability of photosystem II to photodamage and hence necessitates the rapid turnover of the D1 protein of the reaction center.

Fabaceae↗
PubMed1994

Identification of two cardiac glycosides as Na(+)-pump inhibitors in rat urine and diet.

Endogenous Na(+)-pump specific inhibitors are present in the plasma, urine, and tissues of humans and animals. To date, the source of these inhibitors has not been rigorously defined. In the present study, large amounts of several Na(+)-pump specific inhibitors have been demonstrated to exist in the urine of rats raised on a regular chow diet and tap water. All of the inhibitor levels have been found to increase 1.5-8-fold by the surgical preparation of reduced renal mass (RRM) and one-kidney, one-clip (IK, IC) hypertension. These urinary inhibitors, however, except for the ouabain-like inhibitor which eluted from a high performance liquid chromatography C18 column at the same retention time as [3H]ouabain, disappeared within a week after switching the diet from regular diet (number 5001, PMI Feeds, Inc.) to pure synthetic diet (number 5755). The urinary level of the ouabain-like inhibitor decreased to only one-half of the level in the control rat raised on a regular diet. Two of these inhibitors were purified from both urine and diet by a combination of Amberlite XAD-2 adsorption chromatography, reverse phase low pressure liquid chromatography, and several high performance liquid chromatographies. Reverse phase high performance liquid chromatography, liquid secondary ion and gas-liquid mass spectrometries, and proton nuclear magnetic resonance spectroscopy identified these inhibitors as a stereoisomer of convalloside, probably neoconvalloside, and a mono-rhamnoside of periplogenin or its stereoisomer. These cardiac glycosides exhibited inhibitory potencies comparable to ouabain against ouabain-displacement from Na+,K(+)-ATPase and against 86Rb uptake into human erythrocytes, and they also exhibited cross-reactivity to anti-ouabain antibodies and anti-digoxin antibodies. These results clearly demonstrate that the principal source of most of the inhibitors in rat urine is the diet. The results suggest that the ouabain-like inhibitor may be derived from an endogenous origin.

Analysis of Variance↗
PubMed1994

Modulation of mustard toxicity by tacrine.

Compounds containing the chloroethyl group are potent inhibitors of DNA synthesis and cell growth. Tacrine, a choline carrier inhibitor, was found to protect both HeLa cells and rat thymocytes against the effects of nitrogen mustard. DNA synthesis was restored from 13 to 71% of the control value and cell viability restored from 27 to 57% of the control value by exposure of the cells to an equimolar concentration of tacrine immediately prior to nitrogen mustard. In contrast, tacrine was unable to significantly protect rat thymocytes against the toxic effects of sulphur mustard. These results have implications for the clinical use of nitrogen mustard.

Animals↗
PubMed1994

Time-resolved fluorescence spectroscopy and intracellular imaging of disulphonated aluminium phthalocyanine.

Spectroscopic studies were carried out on the photosensitizer disulphonated aluminium phthalocyanine (AlS2Pc) which has prospective applications in photodynamic therapy. The fluorescence lifetimes of AlS2Pc were measured in a range of model systems and cultured leukaemic cells using laser excitation and time-correlated, single-photon-counting detection. In an investigation of non-covalent protein binding, we studied AlS2Pc in the presence of human serum albumin (HSA) in 0.1 M phosphate-buffered saline at pH 7.4. On addition of excess concentrations of HSA, small red shifts in the fluorescence and absorbance spectra were observed, together with an increase in fluorescence polarization anisotropy, consistent with binding of the phthalocyanine. Fluorescence decays could be resolved into two lifetimes for bound AlS2Pc with a dominant component of 5.5 ns and a minor component of 1 ns. Fluorescence imaging and time-resolved microfluorometry were carried out on intracellular AlS2Pc using leukaemic K562 cells. Microscopic imaging with a charge-coupled device (CCD) camera revealed that AlS2Pc fluorescence predominated in a discrete perinuclear region which was then probed selectively by a focused laser spot for fluorescence lifetime measurements. Bi-exponential decays with lifetime components of 6.1 and 2.2 ns were observed. On irradiation at 633 nm, the fluorescence intensity increased initially and subsequently declined due to photodegradation.

Aluminum↗
PubMed1994

Luminescence lifetimes in biological systems.

Photo-luminescence (fluorescence, phosphorescence and delayed fluorescence) can be used as a probe of the molecular environment (polarity, micro-viscosity and mobility), and has very widespread uses in biological systems. Modern laser-based techniques for the measurement of fluorescence decay times in the nanosecond to picosecond time-domain, time-gated fluorescence spectra, and fluorescence anisotropy, are outlined, with recent results on several biological systems with both intrinsic and extrinsic probes used as examples. Anisotropy measurements on fluorescent probes in lipid bilayers and membranes are described and application of this technique to the study of the enzyme subtilisin in natural and modified form is described and application of this technique to the study of the enzyme subtilisin in natural and modified form is discussed in detail. Particular emphasis is placed on studies of surfaces by using the relatively new technique of time-resolved evanescent wave-induced fluorescence spectroscopy, the example here being the study of surface-adsorbed bovine serum albumin, with use of rhodamine dyes as probes. Fluorescence imaging is widely used in medical and biological applications, and several recent developments in three-dimensional confocal techniques are described. The potential of time-resolved fluorescence imaging is explored, and some results are presented on the fluorescence decay of dye in living cells and on the time-gated imaging of these dyes in tissue.

Animals↗
PubMed1994

The use of 32P-postlabelling to detect DNA adducts produced by experimental anticancer drugs: DNA-directed nitrogen mustards.

DNA alkylation by four acridine-linked 'DNA-targeted' aniline mustard derivatives has been studied by 32P-postlabelling. P1 nuclease digestion proved much more efficient than butanol extraction for enhancing the yield of adducted bases for these somewhat hydrophilic compounds. The yield of adducts was maximal after approximately 4 h digestion with micrococcal nuclease/spleen phosphodiesterase and remained relatively constant after that up to 24 h, suggesting that the adducts formed are stable under these conditions. There was some variation in the rates of phosphorylation of the adducts by T4 polynucleotide kinase, with optimal labelling generally occurring after 1 h. The (CH2)5O-linked half-mustard derivative 1 gave five nucleotide 3'-diphosphate adduct spots with calf thymus DNA. Two of these were identified as the adenine N1 and N3 adducts, corresponding to those previously identified as the main base adducts formed by 1 following acid digestion studies. The corresponding full mustard also gave five adduct spots. In contrast, the (CH2)3-linked half-mustard 3 gave only two adduct spots, the most intense of which was identified as a guanine adduct. The corresponding full mustard 4 gave three adduct spots, two of which were identified as guanine adducts. These results agree well with those obtained for the same compounds by the more tedious methods of acid digestion to base adducts, followed by isolation on HPLC, and show that the technique of 32P-labelling can be usefully applied to the study of alkylation of DNA by this class of 'targeted' mustards.

Aniline Mustard↗
PubMed1993

Sequential assignment and structure determination of spider toxin omega-Aga-IVB.

The solution structure of a peptide toxin isolated from funnel web spider venom, omega-Aga-IVB, was determined by 2D NMR methods. omega-Aga-IVB is a high-affinity specific blocker of P-type voltage-dependent calcium channels. Nearly all of the proton resonances of this 48-residue protein were assigned using conventional 2D homonuclear NMR experiments. The three-dimensional structure of the molecule was determined by simulated annealing. The distance and dihedral restraints used in the structure calculations were derived from NOESY and COSY-type experiments, respectively. Mass spectrometric analysis of omega-Aga-IVB suggests that the protein contains four disulfide bonds. In the absence of chemical data to identify the pattern of cysteine pairing, the disulfide bonds of the toxin are proposed from the NMR data and subsequent structural calculations. The structure of the toxin can be described as a three-stranded anti-parallel beta sheet connected by flexible loops. A striking feature of the structure is that the C-terminal 10 residues of this protein adopt random coil conformations. Several positively charged amino acid side chains are found localized on one face of the molecule, in close proximity to the C-terminal tail. This observation has led us to propose a speculative model of the toxins blockade mechanism.

Agatoxins↗
PubMed1993

Characterisation of the photochemotherapeutic agent disulphonated aluminium phthalocyanine and its high-performance liquid chromatographic separated components.

Disulphonated aluminium phthalocyanine (AlPcS2), a potential clinical photosensitiser, has been synthesised in a reproducible form and shown by reversed-phase HPLC to consist of at least eight components which are believed to be individual AlPcS2 regioisomers. These components have been isolated either as single bands or mixtures of two using preparative reversed-phase HPLC methods. The number and position of sulphonate groups per phthalocyanine macromolecule for each component has been determined using a chemical degradation and HPLC assay. Results suggest that the bulk AlPcS2 material consists mostly (> 60%) of an amphiphilic alpha-, alpha-disubstituted regioisomer, with both sulphonate groups substituted to the same side of the molecule (adjacent form). Possible structures for some of the other separated components of AlPcS2 are also presented.

Chromatography, High Pressure Liquid↗
PubMed1993

HECs: are they evaluating their performance?

Although the incidence and composition of HECs has been well characterized, little is known about how HECs assess their performance. In order to describe the incidence of HEC self-evaluation, the methods HECs use to evaluate their performance, and the characteristics of HECs that influence self-evaluation, we surveyed the readers of Hospital Ethics. 290 HECs in 45 U.S. states, the District of Columbia, Puerto Rico and three Canadian provinces, completed questionnaires. Of the 241 HECs included in the data analysis, 97.9% had performed some self-evaluation. Responding committees largely made formative rather than summative evaluations and appeared to evaluate performance in light of their own objectives rather than basing assessments on specific structural, process, and outcome measures of quality. Responding committees used certain evaluation criteria more extensively than others--among these, the number of participants and staff knowledge of the service provided--with the choice of criteria differing with the function being evaluated. Eight characteristics of HECs influenced the probability of self-evaluation, including age, number of beds and meetings, the existence of a mission statement, and a budget. The presence of certain characteristics made HECs six times more likely to evaluate their performance than HECs without the characteristic.

Canada↗
PubMed1993

Inpatient costs of injury due to motor vehicle traffic crashes in New Zealand.

The hospital inpatient costs for the treatment of injury were obtained for Dunedin Hospital for a two-year period using the Resource Utilisation System. These data were used as a basis for estimating national inpatient costs for motor vehicle traffic crashes (MVTCs). The results show that injuries were on average more expensive to treat than non-injuries ($3,115 vs. $2,749 per case). At a mean cost of $5,253 per case, injuries due to MVTCs were the most expensive class of injury event to treat. The average cost of treating a case varied by the class of road user, nature of injury, and severity of injury. Pedestrians were on average, twice as costly to treat as motor vehicle occupants. Costs for treating the late effects of motor vehicle crashes were higher, with a mean cost of $5,695. Internal injuries were on average 4.5 times more expensive to treat than intracranial injuries, the least expensive group of injuries to treat. On average, critical injuries cost 15 times more to treat than minor injuries. The cost of treating pedestrians was disproportionately higher than that for other road users. Nationally pedestrians accounted for 10% of all hospitalised road users, but they contributed 18% of the total cost. Internal injuries had the highest disproportionate cost accounting for 7% of cases and 16% of the costs. Similarly, severe and critical injuries combined accounted for 6% of the national cases but contributed 19% of the national costs. Overall, the leading contribution to the total national cost were made by occupants (43%), lower limb fractures (24%), and moderate injuries (37%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗
PubMed1993

The stability of cardiovascular parameters under different behavioral challenges: one-year follow-up.

The stability of myocardial, peripheral vascular and systolic time-interval measures was assessed over a one-year period in a sample of ten healthy normotensive men. Subjects participated in three laboratory sessions, the first two of which were two weeks apart, and the third approximately one year later. Measures were sampled during the preparation and delivery of a speech, a mirror star tracing task, and the forehead cold pressor test. The results of intraclass correlations computed between the mean of the first two sessions and the third showed that baseline and task levels were highly reproducible across all tasks and most parameters over the one year interval. Results also showed that the long term stability of delta is largely task-dependent.

Adult↗
PubMed1993

Quality assurance for intraoperative transesophageal echocardiography monitoring: a report of 846 procedures.

We evaluated our experience with 846 consecutive transesophageal echocardiography (TEE) intraoperative monitoring procedures performed between November 1989 and July 1991. TEE frequency was 36 +/- 11 per month (range 16-55) and represented 69.8% of cardiac valve surgery cases, 40.2% of coronary artery bypass graft cases, and 2.2% of total operative caseload. Major patient complications consisted of transient vocal cord paresis and ingestion of glutaraldehyde-disinfectant solution. Minor complications consisted of a chipped tooth (one case) and pharyngeal abrasions (three cases). The Quality Assurance (Q/A) Program evaluated both record keeping and quality of imaging, as judged by cardiologist echocardiographer reviewers. The percentage of completion for each Q/A indicator was as follows: medical record documentation, 88%; database form annotation, 94%; and provision of videotape recording, 91%. TEE database forms were analyzed further in terms of the percentage of fields completed. Completion scores were 73%. The following scoring system was utilized for videotape evaluation by the cardiologists: 1 = excellent; 2 = good; 3 = poor. The median grade for both two-dimensional echocardiography and color flow Doppler (CFD) examinations was 2. Poor quality images (grade 3) were present in 15.2% of two-dimensional echocardiography and 20.3% of color flow Doppler examinations, and disproportionately associated with 4/26 attendings. Supplemental audit of the cardiology reviewers performance demonstrated 569/846 videotapes showed no objective evidence of review. The cardiology reviewer forms of the remaining 277 videotapes were evaluated in terms of the percentage of fields completed. The completion score was 56%. These data suggest the need for formal Q/A for intraoperative TEE, both for anesthesiologists and reviewing cardiologists.

Echocardiography↗
PubMed1993

The economics of smoking: an overview of the international and New Zealand literature.

The majority of work to date on the costs of smoking has focused on the enumeration of direct medical care costs. Published estimates of excess medical care expenditure attributable to smoking range from $US54 to $US1058 per smoker per year (1990 prices). Most of these studies used a cross-sectional approach to costing, however consensus increasingly favours the 'life cycle' approach to estimating the costs of cigarette smoking. The life cycle approach to costing consists of tracking all expenditures associated with smoking over the individual's lifetime. The purpose of taking this approach is to separate out the opposite impacts on medical care expenditures of higher utilisation and higher mortality. Thus, in a cross-sectional costing approach, smokers always appear to incur higher medical care costs. Using the 'life cycle' methodology, however, some of the higher medical care costs of smokers are offset by their shorter life expectancy. The policy question is whether smoking is associated with higher healthcare expenditures over the lifetime. The conclusion from studies that have adopted the 'life cycle' approach have been inconsistent. One of the earliest studies, based on Swiss data, concluded that the lifetime medical care costs for a cohort of nonsmokers was equivalent to the costs of providing care for a society of smokers. This conclusion was based on the finding that nonsmokers lived longer than smokers and used medical services more heavily during the last years of their lives.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗
PubMed1993

Photoperiodism in Japanese quail (Coturnix coturnix japonica) with special reference to relative refractoriness.

Cloacal gland (an androgen dependent sex accessory) of Japanese quail exhibits full breeding condition as long as these were maintained under long days (LD 16:8). When shifted to short daylength (LD 6:18), scotosensitivity (cloacal gland regression) was observed up to 5 weeks, followed by scotorefractoriness (cloacal gland development). There was a regression in cloacal gland volume of the birds when shifted to intermediate daylength (LD 13.5:10.5 and 13:11) after 12 weeks of exposure to long days (relative refractoriness) but no regression when shifted to relatively short days (< 14 hr) after 3 weeks of exposure to long daylength. Birds maintained under constant short photoperiod (LD 6:18) exhibited cyclicity. Shift experiments (quail reared and maintained under continuous light; LL, were shifted to LD 16:8, 13:11 and 8:16, similarly quail maintained under LD 16:8 were shifted to rest three photoperiods and so on) made to compare the cloacal gland responses indicated that if the difference between two photoperiods (previous and shifted one) was more the percentage of difference in cloacal gland response was also high. Short daylength (LD 8:16) was always gonadoinhibitory for the quail previously exposed to any daylength (13L, 16L or 24L) and 16L and 24L were always stimulatory for the quail previously exposed to other daylength (8L, 13L, 16L). But, when the birds were shifted to 13L, photoresponses cannot be generalized and it depends on the photoperiod to which quail were exposed previously (i.e. photoperiodic history).

Animals↗
PubMed1992

The costs of smoking revisited.

AIMS: a previous study of the cost of smoking to the New Zealand health services estimated that the excess hospital resource use generated by smoking amounted to $81 million in 1986 dollars. The present study refined and updated the figures for hospital resource use, and extended the costing exercise to include aspects of primary health care. METHODS: excess hospital costs attributable to smoking were estimated from the 1987 national hospital discharge data (both public and private hospitals), and figures obtained from the Otago resource utilisation system (RUS). The costs of excess prescription medicines use and general practitioner consultations were estimated from existing data sources. RESULTS: the excess hospital costs attributable to smoking totalled $128.3 million. A further $37.8 million was consumed in excess prescription medicines use, plus $19.3 million in general practitioner consultations. The total cost to the health services of cigarette smoking was therefore conservatively estimated at $185.4 million (in 1989 dollars). CONCLUSIONS: previous estimates substantially underestimate the external costs imposed by smoking. The figure of $185.4 million contrasts with the $7.5 million of sponsorship support which the tobacco industry is estimated to provide for New Zealand sports. Politicians who intend to repeal Part 2 of the Smokefree Environments Act (1990) should consider these external costs imposed on society by cigarette smoking.

Adult↗