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Biomedical subjects

R A Christian

Publications and source records attributed to R A Christian.

4 recordsLinked to original sources

The binding of topically applied glucocorticoids to rat skin.

The epidermis of rat skin was shown to be the major site of accumulation of label after the topical application of [3H]-cortisol, [3H]-corticosterone and [3H]-triamcinolone acetonide. However, incubation of the skin in vitro in a way which ensured contact only between the dermal side of the skin and the steroid showed preferential accumulation of label from [3H]-cortisol and [3H]-corticosterone in the epidermis whereas label from [3H]-triamcinolone acetonide appeared evenly spread in the dermis and epidermis. The affinity of corticosterone to soluble proteins in skin homogenates was greater than that of cortisol as measured by displacement binding and correspondingly glucose uptake into the skin in vitro was inhibited for 18 hr after a single application of corticosterone but was not inhibited by cortisol.

Administration, Topical

Renal uptake and metabolism of adrenocorticotrophin analogues in the rat: an autoradiographic study.

Renal resorption of tritiated adrenocorticotrophin analogues was studied in the rat using light microscopic and quantitative electron microscopic autoradiography. The synthetic corticotrophins used were Synacthen (corticotrophin-(1-24)-tetracosapeptide) and C41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1-18)-octadecapeptide amide), the tetracosapeptide being tritiated in either the tyrosine residue of position 2 or 23 or the phenylalanine of position 7 and the octadecapeptide in the tyrosine of position 2. Inspection of autoradiographs showed that peptides injected intravenously were resorbed into proximal tubules by endocytosis to produce vesicles whose radiolabel later appeared in lysosomes, a route previously elucidated for other peptides and proteins. The use of two techniques for analysis of electron microscopic autoradiographs, however, suggested that apical tubules also acquire label and are in some way involved in the transfer of resorbed labelled material from endocytotic vesicles to lysosomes. In addition, the autoradiographic analyses revealed that the duration of lysosomal labelling depends upon the position of tritium in the chain. Thus, when the CO2H-terminus of Synacthen was labelled, silver grains were more transiently associated with lysosomes than was the case when the NH2-terminal or core regions were tritiated, indicating a greater resistance of these portions of the peptide to attack by intracellular peptidase. The label from the chemically protected C 41795-Ba was also less readily expelled from the lysosomes of the proximal tubules.

Adrenocorticotropic Hormone

Autoradiographic study of the distribution and cellular uptake of (14C) - streptozotocin in the rat.

The distribution and cellular accumulation, in the rat, of three specifically 14C-labelled forms of streptozotocin were investigated. A significant pancreatic accumulation of radioactivity was observed with (3' -methyl-14C)-streptozotocin only. Autoradiographic studies revealed high levels of bound radioactivity in the islet tissue following the administration of (3 -methyl-14C)-streptozotocin whereas much lower levels of radioactivity were detected in the pancreatic tissue following the administration of either (1-14C)-streptozotocin or (2' -14C)-streptozotocin. In the pancreasea, the amount of radioactivity bound to islet tissue was always significantly higher than that bound to acinar tissue. In addition to the islet tissues, the kidney cortex showed a very high level of bound radioactivity after the administration of (3' -methyl-14C)-streptozotocin. The results suggest that streptozotocin is rapidly metabolised by the rat. The apparent specificity for the accumulation of radiolabel from (3' -methyl-14 C)-streptozotocin suggests that a metabolite derived from the methyl bearing ureido side chain of the drug may be specifically involved in the induction of tissue damage and the consequent development of diabetes.

Animals

A novel approach for enzyme histochemical and autoradiographic studies on single cells.

A simple technique that does not involve the use of heat has been developed to fix cells or cell organelles. The cells or organelles are mixed with a bovine serum albumin solution, gelled by the addition of a suitable fixative, and then either embedded or frozen. The gelled mixture contains well preserved cells or organelles that are evenly dispersed, thus eliminating the problems of pellet packing. The technique was excellent for ultrastructural autoradiography where radioactive materials bound to plasma membranes or cytoplasmic nucleotides were being studied. Histochemical tests could be applied to the fixed embedded material. Light and electron microscopy could be done on the same well-mixed sample. Fixed frozen albumin samples cut with ease on a cryostat but there was ice crystal formation.

Adrenal Glands