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Biomedical subjects

R G Brown

Publications and source records attributed to R G Brown.

At least 127 records · Page 7Linked to original sources

Alaskan Malamute chondrodysplasia. V. Decreased gut zinc absorption.

Experiements were conducted to determine if zinc absorption was impaired in Alaskan Malamutes which had a genetic chondrodysplasia or dwarfism. When the uptake of an oral dose of 65Zn from the gut in blood was measured in whole dogs it was found that the chondrodysplastic animals absorbed only 25 per cent the amount absorbed by their controls. In vitro studies suggested that 65Zn was initially bound to a protein fraction in all cases but it was later released to a non-protein fraction in the case of normal dogs. This transfer did not occur in the case of the chondrodysplastic dog and it suggests that the transfer of zinc from a protein to a non-protein fraction in the mucosal cell may be the missing step in the dog with chondrodysplasia.

Animals↗

Synthesis of various geometric and enantiomeric oxime O-(alpha- and beta-methylcholinyl) ethers as potential anticholinergic agents.

Various enantiomeric and geometric oxime O-(alpha- and beta-methylcholinyl) ethers were synthesized as potential anticholinergic agents. The synthesis, separation, resolution, and structural characterization of these compounds are reported. The first step of the synthetic pathway involved an oxime formation, with subsequent O-alkylation of the respective oxime with 2-chloro-N,N-dimethylpropylamine hydrochloride. The separation of the alpha- and beta-structural isomers utilized vacuum fractional distillation and/or column chromatography, and the resolution of the enantiomers was accomplished via the formation of tartrate diastereoisomers. A preliminary pharmacological evaluation for anticholinergic activity was conducted using a rat ileum assay. Structure-activity relationships, including some stereochemical properties and antimuscarinic activity, are discussed.

Animals↗

Synthesis and structure-activity relationships of selected isomeric oxime O-ethers as anticholinergic agents.

A series of isomeric (Z)-and (E)-oxime O-beta-dimethylaminoethyl ether methylhalide derivatives was synthesized, and their (Z)-and (E)-assignments were made on the basis of chemical and spectral data. The respective (Z)-and (E)-isomers were evaluated as anticholinergic agents on the rat ileum. The antimuscarinic potencies of the respective (Z)-and (E)-isomers were compared to determine the effect upon potency of this type of geometric isomerism. Three general structure-activity relationships and discernible among the synthesized compounds: (a) among oxime O-ethers derived from aromatic aldehydes, the higher potency consistently resides in the isomer where the aryl substituent is (E) to the ammonium ether substituent; (B) among oxime O-ethers derived from diaryl ketones, the (Z)-and (E)-isomers are approximately equipotent; and (c) oxime O-ethers derived from diaryl ketones are the most potent of the synthesized compounds.

Animals↗

Characterization of a Cytoplasmic Reserve Glucan from Ruminococcus albus.

Ruminococcus albus, an anaerobic bacterium that digests cellulose in the rumen of cattle, produces intracellular polysaccharide granules varying from 0.05 to 0.31 mum in diameter when grown in batch culture. This polysaccharide material was purified and found to contain d-glucose as the only reducing sugar. The polyglucose polymer was slightly opalescent in aqueous solution and formed a strong reddish purple iodine complex with a maximum absorbance at 550 nm. Its infrared spectrum had characteristic absorption bands at 8.70, 9.25, and 9.75 mum and was identical with that of the amylopectin-glycogen type of Megasphaera elsdenii and that of the glycogen of enteric bacteria and beef liver. It reacted strongly with concanavalin A. Methylation analysis showed that the glucan contained 2,3,4,6-tetra-O-MeG-2,3,6-Tri-O-MeG-2,3-Di-O-MeG in a ratio of 8:84:8. Characterization of the products obtained by treatment with isoamylase indicates that the glucan of R. albus is of the glycogen type.

Journal Article↗

Eburicol, lichesterol, ergosterol, and obtusifoliol from polyene antibiotic-resistant mutants of Candida albicans.

Two classes of polyene-resistant mutants were isolated from survivors of N-methyl-N'-nitro-N-nitrosoguanidine treatment of a wild-type Candida albicans. An analysis of the major sterols of one class revealed an accumulation of lichesterol and fecosterol while the other class accumulated eburicol, obtusifoliol, and lanosterol with minor quantities of C28 sterols.

Amphotericin B↗

Alaskan Malamute chondrodysplasia III. Connective tissue of bone.

The dwarf Alaskan Malamute was compared in these studies with normal Alaskan Malamutes of the same age with regard to collagen and mucopolysaccharide components of the bone. The hydroxyproline concentration of bone segments was normal in most instances, whereas, the hexosamine concentration was increased (P less than .05) in distal segments. Alterations in amounts of collagen soluble in neutral salt, dilute acid and 5 M guanidine hydrochloride were observed and these were related to changes in subunits found following chromatography on carboxymethyl (CM) cellulose. The presence of an increased keratosulfate fraction in dwarf Alaskan Malamutes was consistent with an apparent delayed bone ossification process. These changes in the connective tissue moieties may account for the gross morphology with respect to the bowed legs. The primary cause for these changes has not yet been determined but alterations in factors related to processes of normal development in bone are suggested. The present observations tend to support the hypothesis that the changes in the bone are secondary to some other primary metabolic defect.

Animals↗

Alaskan malamute chondrodysplasia IV. Concentrations of zinc, copper and iron in various tissues.

Trace mineral concentrations in various tissues of the chondrodysplastic (dwarf) Alaskan Malamute are remarkably different as compared to normal. The zinc level in heart tissue was depressed in dwarf animals (26 weeks). Copper concentration in the liver is elevated two to four fold in 26 week old dwarf animals and iron levels are significantly elevated in kidney, liver and pancreas of these animals. These observations suggest that the dwarf Alaskan Malamutes suffer from a genetic defect in trace mineral metabolism. If this is the case, then many of the skeletal lesions reported for these animals may be attributed to disorders in either zinc or copper metabolism.

Animals↗

Advanced and recurrent squamous carcinoma of the lower lip.

The results of aggressive surgical treatment of primary lip cancer and advanced and recurrent carcinoma of the lip are illustrated and discussed. Early detection of involved lymph nodes before capsular penetration occurs and careful and complete dissection of the submental and submandibular regions are advocated as possible ways to prevent persistent upper neck disease, the main killer of these patients.

Carcinoma, Squamous Cell↗