Studies on phosphomutases. 3. Phosphoryl transfer to phosphoglucomutase from 1,3-diphosphoglycerate.
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Biomedical subjects
Publications and source records attributed to G K Lam.
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Bartell, Pasquale F. (University of Pennsylvania, Philadelphia), Thomas E. Orr, and Grace K. H. Lam. Polysaccharide depolymerase associated with bacteriophage infection. J. Bacteriol. 92:56-62. 1966.-A recently isolated bacteriophage of Pseudomonas aeruginosa was observed, in association with bacteria, to produce a polysaccharide depolymerase. Exposure of slime polysaccharide to the enzyme at the pH optimum of 7.5 for 30 to 60 min resulted in a decreased viscosity of 20 to 25%, and a measurable increase in the levels of hexosamines, hexoses, and reducing substances, distinguishing it from other phage-associated depolymerases. Like egg-white lysozyme, the depolymerase produced a clearing of mature bacterial lawns, but was shown to be devoid of muralytic activity by turbidimetric and paper chromatographic analysis. The depolymerase reacted with polysaccharides of only certain strains of P. aeruginosa, and there appeared to be no correlation with phage susceptibility. The enzyme was not detectable in uninfected cultures, nor was it synthesized when infection was initiated by phages other than phage 2. The available data suggest that the genetic information required for biosynthesis of this enzyme is furnished by the phage 2 genome.
A general method of formulating tissue equivalent liquid mixtures of a given chemical composition and density using the technique of linear programming is described. It is used to generate mixtures with equivalent atomic composition as ICRP Standard Man and mammalian muscle (NBS Handbook 85) using eight compounds to cover the range of densities from 1.0 to 1.13. Use of the method to handle other parameters of a mixture is also described.
An autoradiographic technique incorporating a new imaging system was used to detect pion-induced radioactivity in Plexiglass and the results were compared with aluminium activation and PET imaging. The activity distribution in the region of the pion-stopping peak was similar in all three cases. Another large signal in the entrance region due to in-flight interactions [12C(pi-, pi- n) 11C] was detected by autoradiography and by PET but was not reflected in the aluminium activation measurements. This new technique is capable of defining the stopping region in phantoms with a better resolution than PET scanning and is useful as a complementary technique to other methods of pion dosimetry.
Treatment planning for conventional radiations is based on the assumption that the effect of a combination of doses at any location in the treatment field in a multibeam plan will be equivalent to that of a single dose made up of the total sum of the doses delivered to that location. This is obviously valid for conventional low linear-energy-transfer (LET) radiations when the dose contributions from various beam components are associated with the same relative biological effectiveness (RBE) value of unity. However, this is not the case for the new generation of charged particle beams whose RBEs have been shown to vary significantly with depth. A concept of effective dose, defined as the mathematical product of physical dose and RBE value evaluated for an effect level, is developed for the treatment planning of these high-LET particle radiations. Based on radiobiological results in mixed radiation experiments, it is shown that these effective doses are linearly additive like physical doses and hence, can be used directly for general treatment planning using linear algorithms already developed for the use of physical doses. This is illustrated using examples of simplified one-dimensional plans for the TRIUMF pion beam.
We evaluated the sensitizing effect of nicotinamide plus carbogen (N&C) and the relative biological effectiveness (RBE) of pions on microscopic tumors where necrotic tumor centers have not yet been established. Female C3H/He mice and SCCVII tumors were used. The irradiation started two days after tumor implantation. In experiment 1, the tumor beds were irradiated at various doses with 250 KVp photons in 5 fractions over 5 days. Nicotinamide (500 mg/kg/mouse/day in 0.2 ml) was injected intraperitoneally (i.p.) 60 min before irradiation, and carbogen (95% O2 + 5% CO2) was flushed at the rate of 10 l/min for 10 min before irradiation and throughout the entire irradiation procedure. In experiment 2, the tumor beds were irradiated at various doses with pions or 250 KVp photons in 10 fractions over 5 days. In both experiments, the mice were observed for 100 days. The rate of tumor appearance was evaluated and the 50% tumor control dose (TCD50) calculated. The sensitizing ratio (SR) of N&C obtained from the TCD50 assay was 1.46 and the RBE of pions was 1.24. The SR of N&C and the RBE of pions were lower for microscopic tumors than those previously reported for macroscopic tumors. These results were probably due to the absence or reduced presence of radiobiological hypoxic component in the microscopic lesion. However, N&C can be considered to provide an advantage for treatment of even clinical microscopic tumors.
Well-known radiotherapeutic strategies for hypoxic cells include hypoxic radiosensitizers, heavy particles, and fractionated irradiation. This study attempted to obtain the ultimate effectiveness of these strategies by combining nicotinamide plus carbogen (N + C) as a hypoxic radiosensitizer with fractionated pions. In addition, the influence on the N + C effect of X-ray dose rate used as a reference radiation was evaluated. When SCCVII tumors in the dorsum of feet reached 50 mm3 in volume, they were irradiated with pions (0.2 Gy/min), the same dose rate (LDR; 0.2 Gy/min) X-rays, or high dose rate (HDR; 1.5 Gy/min) X-rays in 10 fractions over 11 days. Nicotinamide (0.5 mg/g) was administered i.p. one hour before irradiation, and normobaric carbogen (95% oxygen and 5% carbon dioxide) was breathed from 10 min before irradiation. The effect was evaluated by tumor growth time (TGT50) assay. The combination of N + C significantly enhanced the effect of 30 Gy LDR and 28 Gy HDR X-rays, with the effect corresponding to that of 39 Gy HDR X-rays: the enhancement ratios were 1.2 and 1.4, respectively. The effect of 20 Gy pions was equivalent to the effect of 33 Gy HDR X-rays (ratio of 1.65), or the effect of N + C combined with 28 Gy HDR X-rays. However, N + C did not enhance the effect of 20 Gy pions. This suggested that the fractionated pions had great biological effectiveness against hypoxic cells. In conclusion, N + C afforded no additional benefit with fractionated pions, but it was thought to be of value for fractionated X-rays, even in a dose rate of 0.2 Gy/min.
PURPOSE: The purpose of this study was to determine the relative biological effectiveness (RBE) of proton beam and to study its dependency on fraction number. METHODS: The relative biological effectiveness (RBE) of fractionated protons compared with 60Co gamma-rays was investigated for the acute mouse skin reaction. The 80 MeV protons generated at the TRIUMF cyclotron were spread out from 7 to 25 mm to irradiate entire legs. One, two, four, and eight fractions were tested. RESULTS: RBE values ranged from 1.15 to 1.24 for the acute skin reaction. Fraction dose dependence of RBEs was not observed.