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Biomedical subjects

F Ellis

Publications and source records attributed to F Ellis.

At least 19 recordsLinked to original sources

The active site of hemerythrin as determined by X-ray absorption fine structure.

Extensive X-ray absorption fine structure measurements and analysis have been made on azidomet- and methemerythrin and on the native forms of oxy- and deoxyhemerythrin. Due to the availability of models that have been synthesized to mimic the active site of hemerythrin, it was possible to make a thorough assessment of the various errors in the structural parameters determined by the analysis. It is found that the largest source of error is the lack of complete transferability of amplitude and phase between the standards and hemerythrin. This is of particular importance in distinguishing the contributions of the second-shell low-Z atoms and, thus, has a substantial influence on the determination of the iron-iron distance. The internal consistencies of the various checks and a new formulation of error analysis for the structural parameters give us confidence in the structure determined for the active site. The main result is that as O2 is released from oxyhemerythrin, the mu-oxo bridge between the two iron atoms in the active site with an Fe-O distance of 1.8 A converts to a mu-hydroxo bridge in deoxyhemerythrin, expanding the Fe-O distance to 2.0 A. The Fe-Fe distance expands proportionally from 3.24 A in oxyhemerythrin to 3.57 A in deoxyhemerythrin so as to keep the Fe-O-Fe bridging angle approximately constant. These conclusions provide experimental support for the structures of oxy- and deoxyhemerythrin proposed previously on the basis of spectroscopic and preliminary X-ray crystallographic data.

Animals

RBE and clinical response in radiotherapy with neutron beams.

Consideration of the clinical results reported, when a cyclotron produced neutron beam was used for treatments in the pelvis region, suggested that a constant RBE of 3 should not have been used for all neutron doses. Instead a variable RBE, which increased from approximately 3 to 8 (with decreasing dose), should have been used. Although some of these RBE values are much higher than 3, they have been observed in clinical practice. An "equivalent photon" isodose plan was produced by employing a variable RBE and, by taking a TDF limit of 86 for bowel, an isoeffect plan was produced. This shows that in the clinical situation under consideration much of the pelvis was overdosed. Doses to tumour cells and late effects are also briefly considered. It is suggested that, in neutron therapy, both an "equivalent photon" isodose plan and an isoeffect plan should be produced prior to treatment.

Dose-Response Relationship, Radiation

Parenteral depot method for zinc administration.

We have shown that relatively insoluble salts of zinc can be suspended in a benzylbenzoate caster oil vehicle and injected into rats or monkeys from once weekly to once monthly with marked elevation of plasma levels of zinc. The relative water solubility of the zinc salts, at least over the two orders of magnitude of solubility ranges studied, seems not to influence the plasma zinc response. However, a dose-response relationship occurs: the more zinc injected per unit time, the higher the plasma zinc concentrations. In the monkey, the sensitivity of the plasma zinc response increases by approximately one order of magnitude compared to that of the rat, when based upon the dose of zinc injected per kilogram of body weight. This depot method offers advantages over other methods for animal studies of zinc. It may eventually find therapeutic application in man as well.

Animals

Cerebral necrosis following radiotherapy of extracranial neoplasms.

We have examined 6 patients with delayed cerebral necrosis following irradiation of extracranial neoplasms. Four of the 6 patients received 1,760 rets (or less) tumor dose. The initial symptoms attributable to radiation necrosis appeared 4 to 31 months after irradiation and were those of a focal supratentorial mass. Cerebral angiography delineated an avascular frontal or temporal lesion in all 6 patients; in 1 case a magnification study revealed narrowing, irregularity, and occlusion of small cortical vessels. Four of our 6 patients underwent craniotomy with partial or complete surgical extirpation of necrotic brain tissue. Two operated patients are alive and without disabling neurological symptoms 30 and 25 months, respectively, after the operation. The characteristic neuropathological features of delayed radiation necrosis of brain suggest that vascular injury rather than neuronal or glial damage is of primary pathogenetic significance.

Adult

Treatment of connective tissue sarcomas by local excision followed by radioactive implant.

Thirty-two cases of connective tissue sarcoma were treated by local excision immediately followed by a radioactive implant, sometimes supplemented by external radiation. The method is effective in preventing local recurrence, and is particularly valuable for patients in whom persistent local recurrences following simple excision have occurred. The patient experiences little extra discomfort, and complications are unusual; hazard to staff is low. Long-term survival appears to be just as good in our series as in others in which radical surgery was used, the radical surgery has the disadvantages of greater operative morbidity and mortality, causes greater disfiguration, and may in any case be impossible for tumours in certain anatomical sites.

Connective Tissue