Biomedical subjects
D Greene
Publications and source records attributed to D Greene.
Regulation of carboxypeptidase E. Effect of pH, temperature and Co2+ on kinetic parameters of substrate hydrolysis.
Carboxypeptidase E is a member of the carboxypeptidase A and B gene family, with many of the putative active-site and substrate-binding residues conserved between these enzymes. However, the pH optimum of carboxypeptidase E is substantially lower than that of carboxypeptidases A and B. To evaluate whether the difference in the pH optima of these carboxypeptidases reflects fundamental differences in the ionization behaviour of active-site residues, the influence of pH on carboxypeptidase E activity was examined. The V(max) for hydrolysis of dansyl-Phe-Ala-Arg is pH-independent between 5 and 7, but decreases at pH values below 5. The pKa for the group the protonation of which leads to the loss of activity is approximately 4.8, and the slope of the V(max.)/pH profile suggests that only a single ionizable group is involved. In contrast, Km and V(max.)/Km are dramatically influenced by pH over the range 5-7, with multiple ionizable groups detected in this pH range. The pKa of the group the protonation of which decreases the V(max.) of substrate hydrolysis is lower (4.5) for carboxypeptidase E which had been reconstituted with Co2+. The enthalpy of ionization of the group observed in the V(max.) profile for carboxypeptidase E is approx. 28.9 kJ/mol. These results are compatible with the active-site model of the homologous carboxypeptidase A: in this model the ionization of a metal-bound water molecule is responsible for the observed decrease in V(max.).
Standards being developed for assessing and managing stomatitis.
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Glutathione depletion in human and in rat multi-drug resistant breast cancer cell lines.
The effects of GSH depletion in a human breast cancer cell line and a multi-drug resistant subline (ADRr) were determined in a number of experimental conditions. The ADRr cells contained lower GSH concentration which cannot be explained solely on the basis of differences in cell kinetics, and yet the rate-limiting synthetic enzyme gamma-glutamylcysteine synthetase was increased 2-fold. Inhibition of GSH synthesis by BSO resulted in more rapid and more pronounced GSH depletion in ADRr compared to the wild-type cells, suggesting that enhanced GSH utilization and efflux in the resistant cells account for the lowered basal concentration. In addition, the gamma-glutamyl moiety salvage enzyme gamma-glutamyltranspeptidase was reduced markedly in the ADRr cell line. Since these cells have overexpression of the efflux pump protein P-glycoprotein, we examined the effects on cellular GSH of inhibition of the pump's function by verapamil. We found that verapamil significantly depleted cellular GSH. In a rat mammary carcinoma cell line selected in Adriamycin for multi-drug resistance, a similar molecular phenotype has been described including diminished cellular GSH concentration. Verapamil treatment of these cells also resulted in significant depletion of cellular GSH. These results are consistent with the recent report that combined treatment of BSO and verapamil has an additive effect on cytotoxicity. It is likely that decreased basal GSH concentration is due to oxidation and conjugation of it in reactions catalyzed by the enhanced peroxidase and GST found in these cells.
Regulation of carboxypeptidase E (enkephalin convertase).
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Use and perceived efficacy of self-care activities in patients receiving chemotherapy.
Information about chemotherapy side effects and the efficacy of self-care activities used to deal with these side effects is needed to direct nursing interventions for patients receiving chemotherapy. Using the self-care diary (SCD) developed for this study, a sample of 49 adult patients with cancer recorded their side effects, rated the severity of each side effect, and reported on the use and efficacy of self-care activities two days after treatment. Data were collected again five days after treatment to examine the test-retest reliability of the side effect severity component of the SCD. The most common side effect, experienced by 81% of the subjects, was fatigue. Other side effects reported by more than one-third of the subjects were sleeping difficulty, nausea, decreased appetite, and changes in taste or smell. The most frequently reported side effects received mean severity scores indicative of moderate severity. The most commonly used self-care activities were rated as providing some relief to moderate relief of individual side effects. None of the reported self-care activities received mean efficacy ratings that indicated complete side effect relief.
Neutron sensitivity of a carbon-walled CO2-filled ionisation chamber.
In an earlier publication, an expression was derived for the sensitivity of carbon walled, carbon dioxide-filled ionisation chamber, for low-energy neutrons. This expression has been extended to allow its use for high-energy neutrons, and has been used to make detailed calculations for a particular ionisation chamber irradiated with either 15 MeV or 5.5 MeV neutrons. These results of these calculations are compared with experimental values and, within the stated limits, reasonable agreement is obtained.
A sample volume tracking unit for pulsed Doppler echocardiography.
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A fifteen year report of a single tooth replacement system.
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Pain and the hospitalised patient (Part two).
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Operational characteristics of two types of sealed-tube fast-neutron radiotherapy installations.
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Re-irradiation of rat tails to necrosis at six months after treatment with a "tolerance" dose of x rays or neutrons.
Rat tails were re-irradiated to necrosis levels at about six months after various fractionated treatments with 290 kV X rays or 14 MeV neutrons. The X ray dose required to produce necrosis in half of a group of tails (ND50), which had been heavily X-irradiated six months before, was 91+/-4% of the ND50 for aged controls. After prior neutron-irradiation, however, this value was 87+/-4% (neutrons in second treatment) or 75+/-5% (X rays in second course). The "effective" oxygenation of mouse tails at this time after X-irradiation was similar to that of controls; thus these percentage dose values indicate the remarkable tolerance of this organized tissue to a second course of X-irradiation, and the presence of more residual injury in neutron-irradiated tissues.
A transfer instrument for neutron dosimetry.
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Addition of neutron and gamma-ray fractions for intestinal damage.
The microcolony assay technique has been used to test the validty of summing equivalent doses per fraction of 14 MeV neutrons and gamma rays for mouse intestinal damage. For a 4-daily fraction schedule, in which the first one or two fractions are given as neutrons and the remainder as gamma rays, combined dose fractions calculated from a 4-fraction schedule of either radiation type alone produce the same level of damage within the limits of accuracy of the experiment.
Letter: Re-evaluation of published neutron rbe values for mouse intestine.
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Tolerance of rodent tails to necrosis after "daily" fractionated X rays or D-T neutrons.
The rat tail has been used as a model system to study the necrosis of an organized tissue following fractionated doses of collimated D-T neutrons or 290 kV X rays. RBE values for tail tolerance - 10 per cent of tails necrosing after the early skin reactions - rise from about 1-7 (single doses) to about 3-1 (16 fractions in 22 days). Neutron tolerance doses are almost independent of fractionation from 2 to 16 fractions. The tissues at risk are shown to be rather hypoxic. Early skin reaction levels can be used to predict the fraction of tails that will necrose. Early peak reactions for a given fraction of necrotic tails were slightly higher for neutrons than for X rays, and this difference was consistent for all the dose fractionation schedules employed.
The use of a calorimeter for neutron dosimetry.
The dose given to a polythene energy absorber in the radiation field from a 14 MeV neutron generator has been measured calorimetrically. The calorimeter was calibrated by giving the energy absorber a known dose of gamma-rays. The dose measured in this way was compared with that determined with a polythene-ethylene ionization chamber, and the two results agreed to better than 1%, though the estimated uncertainties on the calorimeter and ionization chamber results were each about 4%. This result can be used to determine a value of the ratio Wn/We, for 14 MeV neutrons in ethylene, where Wn is the W value for the charged particles generated in the neutron field in ethylene, and We is the W value for electrons in the same gas. The measured value of Wn/We was found to be 1.07 plus or minus 3.9%. The significance of the 'thermal defect' in polythene is discussed.