Biomedical subjects
Publications and source records attributed to D M Taylor.
Studies with pure LICAM(C) and with its methyl esters showed that all the substances caused increased renal retention of plutonium-238 in the kidneys of mice and rats but were equally effective in reducing plutonium retention in bone and liver.
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The economy of time and effort accruing from the use of laminar air-flow cabinets to obtain germ-free mice has already been established. However, a further modification of the technique, utilizing small intermediate isolators, has made it possible to transfer to the large, recipient isolators only those litters which are viable and demonstrably free from contamination.
Gram-positive bacilli, originating from the diet, are present in the faeces of germ-free mice in this Unit. Although these organisms have never grown on culture and are assumed to be dead it was considered desirable to test this by non-cultural methods because some gut bacteria are difficult or impossible to grow in vitro by present techniques. Germ-free mice were fed a synthetic diet free from live or dead organisms for 10 days during which time the bacilli disappeared from the faeces, re-appearing when the usual diet was re-introduced. This was regarded as confirmation of the non-viability of the bacilli. The use of Wayson's stain for confirmation of non-viability was found to be inappropriate since it produced false-positive reactions with irradiation-killed bacteria.
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The uptake and binding of 59Fe, 67Ga and 239Pu complexed with citrate of transferrin (Tf) and of 125I-labelled Fe-Tf by human lymphoblasts (WI-L2 cells) have been studied. Uptake kinetics of 59Fe-Tf and [125I]-Tf point to internalization by receptor mediated endocytosis. 67Ga binding and uptake is always less. This may be explained by a lower affinity of Ga-complexes for the cell surface. Factors which influence Fe uptake have a similar effect on Ga. 239Pu uptake and binding, however, are different, especially in that Tf does not stimulate 239Pu uptake and may actually decrease it.
The influence of the administered mass on the tissue and sub-cellular distribution of mercury (Hg) was investigated in rats, using 203Hg. The fraction of the dose deposited in liver increased threefold over the dose range 0.17-1.65 mg Hg X kg-1, while the retention in the kidney decreased by a factor of 2. The uptake in other organs, lung, spleen, brain, thymus, salivary glands showed no dose-dependent variation. Subcellular fractionation studies showed a dose-dependent increase in the Hg content of the liver cytosol, with corresponding decreases in the deposition in the lysosomal and nuclei-cell debris fractions. In contrast, no clear changes in the distribution of Hg amongst the subcellular organelles of the kidney were observed. The amount of Hg bound to metallothionein in the liver cytosol rose steeply with increasing dose. However, in the kidney cytosol the mass of Hg bound to metallothionein increased with dose up to 0.55 mg Hg X kg-1, thereafter remaining approximately constant. These observations suggest that the Hg-binding metallothionein in the kidney was saturated by administered doses greater than 0.55 mg Hg X kg-1, whereas in liver saturation levels of the metal were not reached even at the highest dose tested, 1.65 mg Hg X kg-1.
3-(2-[131I]iodobenzoyl)estradiol-17 beta (1), 3-(2-[131I]iodobenzoyl)estrone (2) and 17 beta-(2-[131I]iodobenzoyl)-estradiol (3) have been prepared by bromine-iodine exchange followed by preparative HPLC in radiochemical yields greater than 70% (isolated). The specific activities were greater than 200 Ci/mmol. Tissue distribution studies in DMBA-induced tumor bearing rats showed a rapid clearance via the kidneys and poor accumulation in the target tissues. The relative binding affinities to the estrogen receptor were estimated as 3.5% 1, 1.7% 2 and 0.05% 3 of the affinity of estradiol (100%).
The binding of 239Np(V) to blood serum components of rats was examined in vivo and in vitro. After gel filtration of the serum using a Sephacryl S-300 column, 98% of the applied activity appeared with protein fractions representing coeluted albumins and transferrin. A separation of the albumin- and transferrin-proteins by ion-exchange chromatography using DEAE-cellulose showed the 239Np being entirely bound to the iron-carrier protein transferrin. The high elution yields from the ion-exchange columns, greater than 90%, suggest that the binding may be quite strong. The binding capacity of transferrin for neptunium in vivo was found to decline when the iron level in blood serum was increased. Precipitation experiments showed that 84 +/- 2% of the 239Np was precipitated with 10% (w/v) trichloracetic acid, 77 +/- 3% with 90% ethanol but only 6 +/- 1% with saturated ammonium sulphate at pH 7.4. The available data indicate that as for plutonium, thorium, americium and curium, the iron transport protein, transferrin, may be the main carrier protein for neptunium in mammalian blood serum.
The whole body retention of 181Hf was studied in marmosets (Callithrex jacchus) and found to be closely similar to that in rats and Chinese hamsters. Limited tissue distribution studies suggest a higher uptake in liver and much lower deposition in skin and muscle in the marmoset as compared to the rat or Chinese hamster. Studies in Chinese hamsters showed that treatment with the chelating agent diethylenetriaminepentaacetic acid resulted in only a small reduction in the whole body retention of 181Hf. The absorption of orally administered 181Hf, in various chemical forms, was found to be between 0.04 and 0.13% of the ingested dose and was unaffected by age between 5 and 21 months but was increased by fasting. The measured absorption of 181Hf in Chinese hamsters and in rats was similar to that of plutonium suggesting that radiohafnium could be used as a surrogate for plutonium for selected studies in human volunteers.
Over a period of several months, 5 germ-free mouse isolators became monocontaminated with seemingly the same fastidious, anaerobic bacilli which defied identification. The organism originated in rodent diet which had been exposed to gamma-irradiation. However, it was discovered retrospectively that the irradiation doses had not been monitored, and subsequent monitoring showed the desired dose of 5 Mrad was not achieved in some parts of the load. Although inadequate sterilization was the likely cause of contamination it was not possible to explain why only this fastidious anaerobe survived the treatment, and not other more common bacterial contaminants.
Because MM male mice suffer from a high incidence of urinary tract infection, an assessment was made as to whether the urethral plugs, which occur in male rodents, might be involved in its aetiology. When killed, males more commonly retained urine in their bladders than females but there was no significant difference between strains or method of killing. Males also voided urine more often during stressful handling followed by abdominal pressure, but also retained some urine more often than females. The study of sexually immature mice demonstrated no sex differences and no urine was retained in any bladder. It was concluded that the high frequency of urine retention in mature males is attributable to the presence of urethral plugs but these could not be implicated in the cause of MM urinary tract infection because of comparable findings in the controls. However, the possibility was considered that the plugs might facilitate infection of the kidneys once a bladder infection had become established.
The retention of 67Ga, 203Hg, 175 + 181Hf, 239Pu and 241Am in turpentine-induced abscesses and in normal muscle has been studied in rats for periods of up to 126 days after radionuclide injection (129 days after turpentine). The results show that although the uptake of 203Hg is about 7 times greater in the abscess than in control muscle, the half time of the nuclide is similar in both tissues, T1/2 = 5 days. The remaining radionuclides studied all show a similar retention time in control muscle, average T1/2 = 12.5 days, and a more prolonged retention in the abscess tissue, average T1/2 = 47 days, although in both control and abscess tissue the uptake of the radionuclides showed quite large metal-specific variations. It is concluded that for radionuclides which are transported on transferrin in the blood and which deposit in lysosomes within cells a common metal clearance mechanism may operate in normal muscle and a second general mechanism may operate in abscess tissue. The radionuclide concentration difference between normal and abscess tissue ranged from 8 (67Ga) to 27 (239Pu); thus the radiation dose delivered to the inflamed tissue was between about 30 and 100 times greater than in normal muscle.
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The labelling of blood cells in vitro for subsequent in vivo studies was one of the earliest applications of radioactive tracers in clinical medicine and laid the foundations for many important contributions to the advancement of knowledge of human blood cell pathophysiology. The characteristics required for satisfactory clinical studies, the mechanisms of cell labelling, the problems of radiation of chemical damage to the labelled cells and some examples of modern clinical applications are described and discussed.
The incidence of clinically significant cystoid macular edema (CME) following cataract surgery has risen sharply with the widespread utilization of intraocular lenses. To evaluate the factors contributing to the incidence of CME, the senior author has divided 1808 of his own cataract cases into three groups according to procedures used: 1) intracapsular cataract extraction (ICCE) with no lens implantation; 2) ICCE with implantation of an iris-supported lens; and 3) extracapsular cataract extraction (ECCE) with implantation of a posterior chamber lens. The incidence of CME in these three groups was 2%, 9.9%, and 1.2%, respectively. Contributing factors and visual outcome in all three groups are reviewed. It is concluded that many of the problems associated with ICCE and iris-supported lens implantation seem to be eliminated with the ECCE-posterior chamber IOL procedure. However, it is emphasized that careful longterm follow-up is required to determine safety.