Biomedical subjects
Publications and source records attributed to J S Fowler.
A new fluorimetric method to assay HGPRT (hypoxanthine-guanine phosphoribosyl transferase, EC 2.4.2.8) from human red cell lysates using 6MP (6-mercaptopurine) as substrate is described. This assay is compared with an existing spectrophotometric method using hypoxanthine as substrate. Precision, sensitivity limits and kinetic differences of these assays are reported.
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The syndrome is a condition of poor weight gain and weakness. Changed eating habits of animals suffering from it lead to consumption of a poorly-balanced diet. By softening the diet and avoiding less nutritious foods, the eating habits can be improved and the syndrome halted. Particular attention should be paid to the palatibility of high-protein foods when weaning marmosets.
The relative merits of the automated, fluorimetric assay of urinary enzymes and cell exfoliation were compared with other commonly used tests for renal damage. Two types of nephrotoxic agent were used, causing crystal nephropathy and acute tubular necrosis respectively. Groups of marmosets were given one of two drugs known to cause crystal nephropathy. One agent caused intermittent increases in urinary enzyme excretion and an early increase in cell excretion which was not sustained. The second agent in contrast caused elevated cell and enzyme excretion, increasing throughout the period of administration. A nephrotoxic anti-tumour agent also caused increases in cell and enzyme excretion when given to marmosets. The early changes produced by this agent were studied using catheterised rats. Hourly samples of urine were collected and urinary beta-glycosidase excretion was found to give an early indication of renal damage, which correlated with albuminuria and glycosuria. The fluorimetric assay of urinary enzymes provides a sensitive, non-invasive test of nephrotoxicity.
N-Acetyl-beta-D-glucosaminidase activities were determined in homogenates of marmoset kidney, in serum and in urine by using the 4-methylumbelliferyl substrate. The enzyme activity was separated into several components by DEAE-cellulose ion-exchange chromatography, starch-gel electrophoresis and isoelectric focusing. The kidney contained two major forms of the enzyme, A and B, which had similar pH optima and Km values. The A-form bound to DEAE-cellulose at pH 6.8, migrated towards the anode on starch-gel electrophoresis and had a pI of 5.0. The B-form did not bind to DEAE-cellulose at pH 6.8, remained near the origin on starch-gel electrophoresis and had a pI of 7.64. The isoenzymes also differed in heat stability, the B-form being the more stable. Serum contained B-form activity and, in addition, two intermediate forms (I1 and I2) were loosely bound to DEAE-cellulose. The serum A-form activity was less firmly bound to DEAE-cellulose than was the tissue A-form and was designated As. Serum from a pregnant marmoset contained a form which may be analogous to the human P-isoenzyme. Urine contained only a small amount of B-form activity, the majority being present in the A-form. The kidney A- and B-forms both had mol.wts. of 96000--100000 and the activity was predominantly lysosomal. Partial purification of the kidney A isoenzyme was undertaken. Immunoprecipitation studies indicated a relationship between marmoset kidney A-form and human liver A-form activity.
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1. A cheap, robust, radioactive source in sheet form has been designed and constructed from commercially available material. Log-related isotopic dilutions of the source have been used to prepare a Standard Radioactive Scale. 2. The Standard Radioactive Scale has been developed as a method of internal standardization of whole-body autoradiography and its use as an aid to quantitative determination is discussed. 3. The distribution of radioactivity in the sheet source is sufficiently uniform to allow its use for high resolution radiography of thin specimens. This radiographic technique has been applied to whole body sections to demonstrate differences in quenching by tissues and to examine calcification in the rat foetus.
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Explore the source record for details and available documents.
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18F-2-Deoxy-2-fluoro-D-glucose (18FDG) is rapidly extracted by the mouse heart, and the radioactivity in heart (3-4% per organ) remains relatively constant for 2 hr post injection. The brain uptake (2-3% per organ) remained relatively constant throughout the time course of the study. Liver, lungs, kidneys, small intestine, and blood all showed a rapid clearance of radioactivity after injection of 18FDG. At 120 min the heart-to-lung ratio was 12 and heart-to-liver ratio was 32. Urinary excretion of activity was approximately 16% of the injected dose at 60 min. The uptake of radioactivity by dog heart following the intravenous administration of 18FDG was 2.8-4.1% at 60 min and 2.4% at 135 min; it was regionally distributed, the areas of highest activity being the left ventricle and the interventricular septum. The brain activity was 2.1-3.5% at 120 min, with a ratio of gray matter-to-white matter of 2-3:1. Urinary excretion in dogs was 16% and 50% of the injected dose at 60 and 135 min. The chemical form of the activity in the urine, although unidentified, was not 18F-. Cross-sectional images of the myocardium of the dog after intravenous injection of 18FDG were obtained using emission tomography.
A simple halogenated derivative of dopamine, 6-iododopamine (1), has been synthesized using two different methods. These synthetic sequences have been applied to the radiolabeling of 1 with carbon-11, iodine-131, and iodine-123. The tissue distribution of 1 in mice, dogs, and rats was determined. The ratio of radioactivity (%/g) in the adrenal medulla-kidney in dogs increases from 3.45 at 2 h postinjection to 33.3 at 24 h postinjection. Thyroid uptakes in mice, dogs, and rats show that in vivo deiodination of 1 is not significant.
After intravenous injection, 11C-octylamine - HC1 is rapidly sequestered by the rabbit lung. The initial lung uptake during the first minute was 70 +/- 6% of the administered dose, and 40% of the injected dose remained after 15 min. Approximately 12% of the administered radioactivity is exhaled as 11CO2 during the first 30 min.
In order to assess the potential utility of amines labeled with short-lived nuclides as agents for lung imaging and function studies in humans, a series of aliphatic amines (C4-C10 and C13) labeled with carbon-11 (T 1/2 = 20.4 minutes), which decays by the emission of body-penetrating radiation, has been used as a model for studying some basic parameters affecting amine uptake and metabolism by the lung and other tissues in mice. The lung uptake (percentage of dose per organ) of aliphatic amines at 1 minute increased from 2.18 +/- 0.13% for butylamine to 13.33 +/- 0.84% for tridecylamine. Partition coefficients (between n-octanol and pH = 7 buffer) were measured for the C4 through C10 amines and for octanoic acid and octanenitrile. Within the amine series, the partition coefficient correlated with lung uptake. A comparison of a series of compounds all having a carbon chain length of eight but with different functional groups (--NH2, --C=N, --CO2H, --OH) showed that the amino group as well as the relatively lipophilic alkyl group were required for lung specificity. The 11C-aliphatic amines were rapidly metabolized via monoamine oxidase (ultimately to 11CO2). Non-amine metabolites in blood and lungs at 5 minutes postinjection were 95 and 50%, respectively. Pretreatment of mice with iproniazid and with pargyline decreased 11CO2 excretion, and iproniazid significantly increased the radioactivity retained by the brain, lungs and liver at 15 minutes. The rate of 11CO2 excretion depended on carbon chain length (C4 less than C5 less than C6 greater than C7 greater than C8 greater than C9 greater than C10 greater than C13).