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Biomedical subjects

A R Johnson

Publications and source records attributed to A R Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1979

Growth-promoting actions of extracts from mouse submaxillary glands on human endothelial cells in culture.

Extracts of submaxillary glands from two different strains of inbred mice were mitogenic for human endothelial cells in culture. The mitogenic activity of extracts from glands of males of the SWR/J and C57BL/10J strains were equivalent, and the growth stimulating effect was unrelated to renin or esteroproteolytic activity. Mitogenic activity in extracts from SWR/J females was less than that from males, and extracts from C57BL/10J females were inactive. The polypeptide growth factors, epidermal (EGF) and fibroblast (FGF) growth factors, also stimulated replication of endothelial cells. Cells from either umbilical arteries or veins responded to submaxillary extracts, EGF, or FGF with a similar increase in cell number, increase in protein and enhanced uptake of 3H-thymidine. The proliferative response was associated with decreased activity of angiotensin I converting enzyme which is localized on the endothelial surface. Nerve growth factor (NGF) was not mitogenic for endothelial cells. Extracts of submaxillary glands from male mice of either strain contained approximately 20 times more EGF than extracts from females, as determined by immunodiffusion. Mitogenic activity of the extracts was completely inhibited by antiserum to EGF, suggesting that the active component of these preparations is EGF.

Animals↗
PubMed1979

Tumour incidence, growth, reproduction and longevity in female C3H mice fed polyunsaturated ruminant-derived foodstuffs.

Earlier studies with the random-bred Quackenbush mouse strain showed that human-type diets based on linoleic acid-enriched foodstuffs derived from ruminants fed protected polyunsaturated oils have no detrimental effects on growth, reproduction or longevity. Tumour incidence and time of onset of tumour development have now been studied in the inbred, tumour-prone mouse strain C3H, in addition to growth, reproduction and longevity. Mice were fed a polyunsaturated human diet, a conventional human diet, or mouse cubes. The results with C3H mice tended to confirm those with Quackenbush strain mice-growth rates and reproductive productivities were very similar in the two groups eating human diets. Mice on the conventional human diet tended to survive better to about 60 weeks of age than mice on the polyunsaturated diet or the cube diet, after which the mortality rates of the mice on the three diets were similar. The degree of unsaturation of the dietary fat had no significant effect on the incidence of tumours. The tumour incidence was about 40% which, taken in conjunction with the average age of onset (about 80 weeks), suggested that the NIV virus rather than the MMTV virus was responsible. It would appear that the high-fat human diets had no effect on the incidence of mammary tumours caused by this virus.

Animal Feed↗
PubMed1979

Effects of life span feeding of ruminant-derived human diets to rats.

A freeze-dried human diet, based on linoleic acid-enriched food stuffs derived from ruminants, was evaluated and compared with a similarly-prepared diet based on conventional ruminant-derived foodstuffs, using Porton rats in a whole-of-life study. A cereal-based stock diet was used for comparison. Serum biochemical and histopathological examinations were carried out at 0.25, 1.1 and 2.1 years of age and other rats were left until they died of natural causes. Although some diet-specific biochemical differences were noted, triglyceride and cholesterol levels showed changes which were more age-specific than diet-specific. Longevity did not seem to be influenced by quantity or quality of dietary fat. The most common cause of death was a bronchopneumonia at about 2 years of age. Dietary fat also did not affect incidence of tumors. The most common tumor was a pituitary adenoma which occurred most often in females. Only minor causes of death were specific to diet with waxy intra-cardial plaques occurring in less than 5% of rats fed both of the high-fat diets and severe systemic hypertension occurring in rats fed the low-fat stock diet at the same frequency. No deleterious changes were noted that were unique to the linoleic acid-enriched diet.

Animals↗
PubMed1979

Uptake of 125I-labelled C3a by cultured human endothelial cells.

The interactions of C3a anaphylatoxin with vascular endothelium were studied in vitro using human endothelial cells in culture and 125I-labelled human C3a. Cultured endothelial cells took up 125I-C3a in a time- and concentration-dependent manner and inactivated it. Uptake was not associated with binding to specific receptors since the amount of radioactivity accumulated by the cells was not influenced by treatment with excess unlabelled peptide, metabolic inhibitors or by low temperature. Further, we observed that uptake was not saturated during 90 min of incubation or within the concentration range of C3a tested (10(-9)--10(-6) M). C3a was taken up more rapidly than other labelled, less basic compounds, including Tyr5-bradykinin, lysozyme and albumin. Examination of the cells by autoradiographic electron microscopy revealed labelled material within the cell cysoplasm but not within specific intracellular structures, such as vesicles or vacuoles. C3a was partially inactivated after incubation with endothelial cells for 15 min, but some spasmogenic activity was retained even after 90 min incubation. Since the peptide is readily inactivated by the cells, the radioactivity in the cytoplasm may be inactive C3a and possibly C3a fragments. The combination of uptake and inactivation of C3a by endothelial cells may be an effective means of removing the peptide from circulation.

Anaphylatoxins↗
PubMed1979

Growth, reproductive productivity and longevity of mice fed polyunsaturated ruminant-derived foodstuffs.

The effects on the well-being of mice of feeding linoleic acid-enriched foodstuffs derived from ruminants receiving protected polyunsaturated oil were determined. Growth, reproductive productivity and longevity were compared in mice fed freeze-dried human diets containing either these products or the corresponding conventional ruminant-derived foods. A laboratory mouse pellet diet was used as a standard for the comparison. Growth rates and life spans were found to be similar in all three groups. Although the reproductive productivity of the mice on the polyunsaturated diet was never significantly different from that of mice on the conventional human diet, productivities of both groups on human diets were usually significantly below those of mice eating pellets. By the third generation of the second reproduction study, productivities of both these groups of mice had returned to the same level as those of mice eating pellets. Possible reasons for the depression in reproductive productivity in mice on the human diets are discussed. It was concluded that the polyunsaturated human diet neither impaired nor improved the lives of the animals eating the diet relative to the lives of animals eating the conventional human diet.

Adipose Tissue↗
PubMed1978

Renal inactivation of substance P in the rat.

The activity and distribution of substance P-catabolizing enzyme(s) were studied in the rat kidney. Kidney homogenates inactive substance P 5-20 times as fast as do homogenates of intestine, liver, lung, heart or brain. The catabolizing activity was highest in the cortex and decreased progressively down the papilla. Cortex of rat kidney was homogenized and fractions enriched in microsomal membrane, final supernatant, plasma membrane, endoplasmic reticulum, brush border and intact glomeruli were prepared. The identity and homogeneity of the preparations were determined by assaying marker enzymes and by morphological examination. Substance P was catabolized most rapidly by the microsomal and plasma-membrane-enriched fractions, and least rapidly by endoplasmic reticulum or final supernatant fractions. Purified brush border of proximal tubules inactivated substance P more than 10 times as fast as isolated glomeruli. Our experiments show that substance P is catabolized at a rate that is similar to the rates of inactivation of bradykinin and angiotensin II. Further, the distribution of substance P-catabolizing activity in various kidney fractions is similar to the distribution of kininase and angiotensinase activities previously reported.

Animals↗
PubMed1977

Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.

Cultured endothelial cells provide a model for the study of interactions of vasoactive peptides with endothelium. Endothelial cell cultured from veins of human umbilical cords contain both angiotensin I converting enzyme (kininase II) and angiotensinase activities. Intact monolayers of cells can both activate angiotensin I and inactivate bradykinin when the peptides are added to culture flasks in protein-free medium. Intact suspended cells or lysed cells convert angiotensin I to angiotensin II, inactivate bradykinin, and hydrolyze hippuryldiglycine to hippuric acid and diglycine. These actions are inhibited by SQ 20881, the specific inhibitor of converting enzyme. The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme. Endothelial cells also inactivate longer analogs of bradykinin, such as kallidin, methionyl-lysyl bradykinin, and bradykinin coupled covalently to 500,000 mol wt dextran. The endothelial cells retained converting enzyme activity through four successive subcultures, indicating that the enzyme is synthesized by the cells surface, and it is apparently a marker for endothelial cells, since cultured human fibroblasts, smooth muscle cells, and baby hamster kidney cells do not have it. Endothelial cells also contain an aminopheptidase which hydrolyzes both angiotensin II and the synthetic substrate, alpha-L-aspartyl beta-naphthylamide. The angiotensinase activity increased when the cells were lysed, which suggests that the enzyme is localized within the cells, Hydrolysis of both alpha-L-aspartyl beta-naphthylamide and angiotensin II was inhibited by omicron-phenanthroline, indicating that the enzyme is an A-tipe anigotensinase.

Angiotensin II↗
PubMed1977

The effects of inorganic ions situated at the enamel surface on the adsorption and activity of acid phosphatase.

This study has demonstrated, first, that the affinity of the enamel surface for a biologically active protein-in this case, acid phosphatase-may be modified by first impregnating the mineral with particular inorganic ions. Second, enzymic activity is altered as a function of the inorganic ion incorporated into the enamel surface. Third, strong inhibition of acid phosphatase is demonstrated by ions expected to be released during the carious process which contradicts the postulation that phosphatases are actively hydrolyzing enamel matrix-bound phosphate during the carious attack. Fourth, these results suggest that by incorporating a particular ion into the enamel mineral, a surface with assigned properties may be created which offers some degree of control over subsequent adsorption of organic matter. Thus, it is apparent that by proper selection of inorganic ions and organic macromolecules, both structural properties and biological activities at the enamel-oral fluid interface may be predictably modified.

Acid Phosphatase↗
PubMed1976

Effects of protected cyclopropene fatty acids on the composition of ruminant milk fat.

Unsaturated fatty acids can be protected from ruminal hydrogenation, and when fed to lactating ruminants, the constituent acids are incorporated into milk triacylglycerols. By this means, it has been possible to reduce the melting point of milk triglycerides and to make softer butter fat. This report shows that, by feeding small amounts of protected cyclopropene fatty acids, one is also able to make harder butter fat. Sterculia foetida seed oil, a rich source of cyclopropene fatty acids, was emulsified with casein and spray dried to yield a free flowing dry powder. When this material was treated with formaldehyde and fed to lactating goats(ca. 1 g cyclopropene fatty acids per day), there were substantial increases in the proportions of stearic acid and decreases in the proportions of oleic acid in milk fat. Similar results were obtained when the formaldehyde-treated supplements were fed to lactating cows (ca. 3 g cyclopropene fatty acids per day). The effect was considerably less apparent when the S. foetida seed oil-casein supplement was not treated with formaldehyde, suggesting that cyclopropene fatty acids are hydrogenated in the rumen as are other unsaturated fatty acids. The effect of feeding protected cyclopropene fatty acids on the stearic:oleic ratio in milk fat is probably due to cyclopropene-mediated inhibition of the mammary desaturase enzymes.

Animals↗
PubMed1976

Autoxidation in milk rich in linoleic acid. II. Modification of the initiation system and control of oxidation.

Factors contributing to the initiation of lipid oxidation in cow's and mare's milk containing high levels of polyunsaturated fatty acids were studied. Addition of H2O2 just after milking, in slight excess of the stoichiometric amounts required to destroy ascorbic acid, delayed the development of oxidized flavours in cow's milk high in linoleic acid. Hydrogen peroxide treatment followed by the addition of alpha-or gamma-tocopherols prevented lipid oxidation in cow's milk even when 0.1 mg Cu/l milk was added. When used separately in the presence of Cu these treatments were ineffective as was butylated hydroxyanisole treatment. The lipid and ascorbic acid in mare's milk were remarkably stable to oxidation. Addition of 0.05 or 0.1 mg Cu/l, ethylenediamine tetraacetic acid, neocuproine, or H2O2 had very little effect on the loss of ascorbic acid and lipid oxidation in mare's milk.

Animals↗
PubMed1976

Fatty liver and kidney syndrome in chicks. I. Effect of biotin in diet.

Fatty liver and kidney syndrome, a disorder of young chicks, was studied under laboratory conditions. Affected chicks had enlarged livers (hepatomegaly), an increased content of lipid in the liver, and an increased level of palmitoleic acid in the liver lipids. The disorder was observed mainly in chicks from young parent flocks, and was associated either with commerical diets which were subsequently found to be low in biotin, or with specially formulated low-biotin diets. A third factor, imposition of stress, was required to initiate the disorder. There was evidence of increased lipogenesis causing an increase of triacylglycerols in the liver lipids and an increased production of saturated fatty acids, particularly palmitic acid. Increased levels of palmitoleic acid resulted from an increased desaturation of palmitic acid. Under stress, affected chicks had low blood glucose levels, suggesting that gluconeogenesis was impaired. Since biotin-dependent enzymes are involved in both gluconeogenesis and lipogenesis, it would appear that the relevant enzymes respond differently to a deficiency of biotin.

Animals↗
PubMed1976

Fatty liver and kidney syndrome in chicks. II. Biochemical role of biotin.

The role of biotin-dependent enzymes in the fatty liver and kidney syndrome of young chicks was studied. Under conditions of a marginal deficiency of dietary biotin, the level of biotin in the liver has differing effects on the activities of two biotin-dependent enzymes, pyruvate carboxylase and acetyl-CoA carboxylase. The activity of acetyl-CoA carboxylase is increased, but when the dietary deficiency of biotin produces biotin levels which are below 0-8 mug/g of liver, the activity of pyruvate carboxylase may be insufficient to completely metabolize pyruvate via gluconeogenesis. There is an increase in liver size and in the activities of enzymes involved in alternate pathways for the removal of pyruvate. Blood lactate accumulates and there is increased synthesis of fatty acids, and an accumulation of palmitoleic acid; these steps are accomplished by increased activities of at least the following enzymes: acetyl-CoA carboxylase, malate dehydrogenase (decarboxylating) (NADP+) and the desaturase enzyme. When the biotin level is below 0-35 mug/g of liver and the chick is subjected to a stress, physiological defence mechanisms of the chick may be inadequate to maintain homeostasis and they finally collapse, resulting in accumulation of triacylglycerol in the liver and blood; the chick is unable to maintain blood glucose levels and death occurs, often only a few hours after the imposition of the stress.

Acetyl-CoA Carboxylase↗
PubMed1976

Gas-liquid chromatography of ethyl ester artifacts formed during the preparation of fatty acid methyl esters.

Ethanol is typically used as a stabilizer in chloroform. Failure to remove this ethanol from the chloroform used in the extraction of lipids leads subsequently to the formation of ethyl ester artifacts during the preparation of methyl esters by a commonly employed transesterification procedure. Depending on the conditions and phases used during gas-liquid chromatography, the ethyl esters may be resolved from the corresponding methyl esters. The resulting chromatograms contain extraneous peaks and may be incorrectly identified.

Chemical Phenomena↗