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Biomedical subjects

J A Olson

Publications and source records attributed to J A Olson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Angiotensin-II induction of plasminogen activator inhibitor-1 gene expression in astroglial cells of normotensive and spontaneously hypertensive rat brain.

Angiotensin-II (AII) stimulates plasminogen activator inhibitor-1 (PAI-1) gene transcription, translation, and protein secretion from astroglial cells derived from normotensive [Wistar-Kyoto (WKY)] rat brain, an effect mediated by AII type 1 (AT1) receptors. Since abnormal expression of the brain AII system has been demonstrated in spontaneously hypertensive (SH) rats, we investigated the regulation of PAI-1 gene expression by AII in astroglial cells from the brains of these animals. AII caused an increase in PAI-1 gene expression in SH rat astroglia in a manner similar to that observed in WKY-derived cultures. However, both the basal and AII-stimulated levels of PAI-1 mRNA in SH rat astroglia were only 20% of those observed in WKY rat astroglial cultures. Consequently, there was a significant reduction in the de novo synthesis and secretion of PAI-1 from astroglia of SH rat brain. The reduced synthesis and secretion of PAI-1 from SH rat brain astroglia was associated with lower numbers of AT1 receptors in these cells. However, the steady state levels of AT1 receptor mRNA were comparable in both WKY and SH rat astroglia. This reduction in AII-modulated PAI-1 levels in SH rat astroglia is consistent with a proposed role of these interactions in the development of hypertension in these animals.

Angiotensin II↗
PubMed1992

Antioxidants in health and disease: overview.

Molecular oxygen is an essential nutrient for higher forms of life. In addition to its normal physiological reactions, oxygen and its partially reduced forms can oxidize a variety of macromolecular and simpler compounds in cells and fluids of the body. Such oxidized and peroxidized compounds have been associated with, and may be causally related to, a variety of chronic diseases. As a protection against excessive oxidation, nature has developed a complex set of interactive antioxidant systems. Selected aspects of antioxidant actions are considered in this symposium.

Animals↗
PubMed1992

Anticoccidial efficacy of semduramicin in battery studies with laboratory isolates of coccidia.

The anticoccidial activity of semduramicin against laboratory isolates of five species of poultry Eimeria was investigated. In laboratory scale battery trials, semduramicin at 20 to 30 ppm demonstrated broad-spectrum anticoccidial efficacy equivalent to salinomycin at 60 ppm. Also, semduramicin at 25 ppm was fed to uninfected cockerels in batteries for 21 days, and growth rate and feed efficiency were found to be equivalent to birds fed salinomycin at 60 ppm. Semduramicin was well tolerated when coadministered with tiamulin. Semduramicin demonstrated the same activity whether produced by semisynthesis or by direct fermentation.

Animals↗
PubMed1992

Chemical synthesis, growth-promoting activity, and metabolism of all-trans retinyl beta-glucose in the rat.

Reaction of all-trans retinol with alpha-D-glucopyranosyl bromide tetrabenzoate in the presence of silver carbonate gave all-trans retinyl beta-glucose in good yield. Depending on the mode of administration, retinyl beta-glucose, which is soluble in water, showed 67-100% of the growth-promoting activity of retinyl acetate in vitamin A-deficient rats. In metabolic studies on vitamin A-deficient rats, retinyl beta-glucose was rapidly hydrolyzed to retinol. The possible therapeutic uses of retinyl glucose are discussed.

Animals↗
PubMed1992

Retinoid glucuronides do not interact with retinoid binding proteins.

Retinoid glucuronides have recently been described as water soluble, biologically active retinoids. In mouse mammary gland organ cultures retinoyl glucuronide, a retinoic acid counterpart, inhibited hormone induced differentiation. In this report we examined whether the effects of retinoyl and retinyl glucuronides are mediated by specific retinoid binding protein in mammary glands in organ culture. Results indicated that neither retinoyl nor retinyl glucuronide competed for cytosolic retinoic acid or retinol binding proteins respectively. These results indicate that either the effects of retinoid glucuronides are independent of retinoid binding proteins or they have to be metabolized to an active component which may in turn bind to retinoid binding protein for the glucuronide action.

Animals↗
PubMed1991

Metabolism in vivo of all-trans-[11-3H]retinoic acid after an oral dose in rats. Characterization of retinoyl beta-glucuronide in the blood and other tissues.

Soon after [11-3H]retinoic acid (RA) (1.1 x 10(8) d.p.m.) was administered orally to rats either as a large dose (115 micrograms = 0.38 mumol/rat) or mixed with unlabelled RA as a huge dose (22 mg = 73.33 mumol/rat), retinoyl beta-glucuronide (RAG) was identified and characterized as a significant metabolite in the serum and small intestine. Of the administered dose, 70% remained unchanged as retinoic acid in the stomach up to 1 h. Significant amounts of 5,6-epoxyretinoic acid, 4-hydroxyretinoic acid, esters of retinoic acid and several polar retinoids, including 4-oxoretinoic acid, were also detected in the stomach. No significant difference was observed in the nature of the retinoids found after a large or a huge dose; however, the ratio of RAG/RA was higher after a huge dose than after a large dose. Thus RAG, which is biologically active in vivo and in vitro, is formed quickly in significant amounts in tissues after a dose of RA.

Administration, Oral↗
PubMed1991

Angiotensin II induces secretion of plasminogen activator inhibitor 1 and a tissue metalloprotease inhibitor-related protein from rat brain astrocytes.

The present study investigates angiotensin (Ang) II effects on secretory protein synthesis in brain astrocytes cultured from neonatal and 21-day-old rats. Ang II-induced changes in the de novo synthesis of [35S]methionine-labeled secretory proteins were visualized using two-dimensional NaDodSO4/PAGE. Astrocytes from 21-day-old rat brain possess specific high-affinity receptors for Ang II. These cells express two Ang II-induced secretory proteins with Mr 55,000 (AISP-55K) and Mr 30,000 (AISP-30K), which were time- and dose-dependent (EC50, 1 nM). [Sar1, Ile8]Ang II (where Sar is sarcosine) inhibited Ang II-induced secretion of AISP-55K but not AISP-30K. N-terminal amino acid sequencing indicates that AISP-55K is identical to rat plasminogen activator inhibitor 1, whereas AISP-30K exhibits 72-81% identity to three closely related proteins: human tissue inhibitor of metalloproteases, a rat phorbol ester-induced protein, and the murine growth-responsive protein 16C8. Immunofluorescent staining with rat plasminogen activator inhibitor 1 antibody was induced in the majority of cells in culture after Ang II treatment of astrocytes from 21-day-old rat brains. Absence of this response to Ang II in astrocytes from neonatal rat brain provides evidence that this action of Ang II on astrocytes is developmentally regulated.

Aging↗
PubMed1991

Induction of HL-60 cell differentiation by water-soluble and nitrogen-containing conjugates of retinoic acid and retinol.

Retinoids induce the promyelocytic cell line, HL-60, to differentiate along the granulocytic pathway in vitro. A number of water-soluble and nitrogen-containing retinoids were synthesized in our laboratory [retinoyl-glucose (RAGL), retinyl-glucose (ROGL), retinoyl-adenosine (RADS), retinoyl-adenine (RAD), retinoyl-beta-glucuronide (beta RAG), and retinoyl-alpha-glucuronide (alpha RAG)]. These retinoids (10(-5) to 10(-8) M), as well as retinoic acid (RA) and retinol (ROL), were tested for their ability to induce the differentiation of HL-60 cells in vitro and to affect cell growth and viability during a 24- to 72-h incubation period. Differentiation was assessed by measuring the percentage of cells expressing the Mac-1 antigen on their cell surfaces. RA and the conjugates of RA were all quite active in inducing HL-60 cell differentiation, whereas ROL and ROGL had much less activity at equimolar concentrations. beta RAG, alpha RAG, RADS, and RAD were less toxic, whereas the glucose conjugates of retinol and retinoic acid (ROGL and RAGL) were both considerably more toxic than either RA or ROL at equimolar concentrations. All retinoids affected cell growth in a dose-dependent fashion. At 24 h, free RA or ROL was not detected in the cells after incubation with any of the retinoid conjugates.

Cell Differentiation↗
PubMed1991

Retinoids and carotenoids in bovine pineal gland.

The retinoids and carotenoids in bovine pineal gland were analyzed by high-performance liquid chromatographic methods. The major retinoid observed was all-trans retinol, with an average level of 579 pmol/g wet tissue. In agreement with a previous report, retinal was not detected; however, we could not detect any retinyl ester in bovine pineal gland. Methods similar to those used in studying metabolism of vitamin A in the bovine eye were used to study the esterification and isomerization reactions of retinoids in the pineal gland. Neither esterification nor isomerization reactions occurred. These results suggest that the key retinoids and enzymes involved in visual function are absent in the bovine pineal gland. The major carotenoid, which has not previously been reported in pineal gland, was beta-carotene at an average level of 1830 pmol/g wet tissue.

Animals↗
PubMed1991

Effects of retinoid glucuronides on mammary gland development in organ culture.

Retinoyl beta-glucuronide (RAG) and retinyl beta-glucuronide (ROG) inhibit prolactin-induced morphological developments in cultured mouse mammary gland, and are equally effective in depressing prolactin and steroid hormone-induced DNA synthesis in the same tissue. Retinol is essentially inactive by both assay methods. Although RAG and ROG show little or no toxicity in several cell and animal models, some possibly toxic manifestations were seen at higher concentrations in cultured mammary tissue. Nonetheless, because of the strong correlation between the actions of chemopreventive agents in culture mouse mammary glands and their effectiveness in vivo, the retinoid glucuronides may well prove to be useful cancer chemopreventive agents.

Animals↗
PubMed1991

Developmental expression of rat insulin-like growth factor binding protein-2 by astrocytic glial cells in culture.

Brain astrocytes were established in primary culture from postnatal and adult rats to characterize the developmental expression of secreted proteins. Astrocytes cultured from 21-day rat brain, but not 1-day rat brain, secreted a distinct group of proteins with Mr of 35,000 as determined by analysis of [35S]methionine-labeled proteins using two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-terminal amino acid sequence analysis of this protein group showed 100% identity to rat insulin-like growth factor binding protein-2 (rIGFBP-2), the BRL-3A IGFBP purified from a fetal rat liver cell line. An antiserum was generated against this astrocyte 35,000 Mr protein, and immunoblot analysis revealed a dramatic increase in rIGFBP-2 secretion in astrocytes cultured from 14-day, 21-day, and adult rat brain compared to astrocytes from 1-day and 7-day rat brain. Similar analysis of neonatal rat brain neurons in culture failed to show immunoreactive rIGFBP-2 in cell lysates or secreted protein. Ligand Western blot analysis demonstrated [125I]IGF-II binding to a single protein band which comigrated with a prominant rIGFBP-2 immunoreactive species in nonreduced conditioned medium from 21-day astrocytes. In comparison [125I]IGF-II binding proteins were detected only at low levels in medium from astrocytes cultured from 1-day rat brain and were undetectable in neuron-conditioned media. Northern blot analysis using a rIGFBP-2 complementary DNA revealed 5-fold greater messenger RNA levels in astrocytes from 21-day rat brain compared with astrocytes from 1-day brain, whereas neonate neurons showed no transcripts. Thus, rIGFBP-2 exhibits a pattern of developmental and cell-specific expression in cultured rat brain cells.

Aging↗
PubMed1991

The reproducibility of the modified relative dose response (MRDR) assay in healthy individuals over time and its comparison with conjunctival impression cytology (CIC).

The modified relative dose response (MRDR) assay is a minimally invasive method of detecting marginal vitamin A status. In the present study, the MRDR assay was performed four times in six well-nourished adults and in one male five-year-old child over a seven-month period. In all instances, assay ratios of dehydroretinol (DR) to retinol (R) were less than 0.03, the tentative cutoff value of 'normal' for the MRDR assay in humans. The mean ratio for all time points for all individuals was 0.015 +/- 0.005, with a mean coefficient of variation of 27 +/- 13%. In a related experiment, both MRDR and conjunctival impression cytology (CIC) tests were conducted on nine adults and the same male child. All DR/R ratios were less than or equal to 0.021, and all CIC specimens were normal. Thus, the DR/R ratio in well-nourished individuals, although showing some variation, does not oscillate between abnormal and normal responses. Furthermore, the DR/R ratios and CIC patterns were fully concordant.

Adult↗
PubMed1991

All-trans retinoyl beta-glucose: chemical synthesis, growth-promoting activity, and metabolism in the rat.

All-trans retinoyl beta-glucose was chemically synthesized in good yield by reaction of retinoyl fluoride with glucose. Retinoyl glucose, which is soluble in water, shows growth-promoting activity similar to retinyl acetate in vitamin A-deficient rats. In metabolic studies, retinoyl glucose was found to be hydrolyzed to retinoic acid, but at a slower rate. The possible therapeutic uses of retinoyl glucose are discussed.

Animals↗
PubMed1990

Site of conversion of endogenous all-trans-retinoids to 11-cis-retinoids in the bovine eye.

By use of a new high-resolution high-pressure liquid chromatographic method for the separation of isomeric forms of retinol, retinal, retinyl ester and retinal oxime, various retinoids were analyzed in separated retinal pigment epithelial tissue or neural retinal tissue from fresh bleached bovine eyes after incubation in the dark at either 30 or 4 degrees C for 90 min. 11-cis-Retinoids significantly increased during incubation at 30 degrees C, relative to those at 4 degrees C, in the retinal pigment epithelium, but not in the retina. The major forms of vitamin A in incubated retinal pigment epithelium and neural retina were retinyl esters (70%) and all-trans-retinol (69%), respectively. Thus, in keeping with observations on the isomerization of radioactive retinol in homogenates of eye tissues, the retinal pigment epithelium seems to be the primary site of 11-cis-retinoid formation from endogenous all-trans-retinoids in the bovine eye.

Animals↗
PubMed1990

The modified relative-dose-response assay as an indicator of vitamin A status in a population of well-nourished American children.

The relative-dose-response (RDR) assay first proposed by Underwood has proved to be a useful indicator of marginal vitamin A status. We suggested that 3,4-didehydroretinol might be used in a simpler assay that requires only one blood sample for analysis. In the present study 24 healthy children aged 3.7-7.1 y were given 100 micrograms 3,4-didehydroretinyl acetate/kg body wt in corn oil, followed by ice cream (90 mL). A blood sample was taken 2, 4, 5, 6, 8, 10, or 24 h after the dose. The mean ratio of dehydroretinol to retinaol (DR-R ratio) plateaued at approximately 0.02 in the plasma between 4 and 10 h. Only three children showed ratios greater than 0.03. Upon reinvestigation, the DR-R ratio remained greater than 0.03 in one child at 5 h. After vitamin A treatment the ratio decreased to 0.019. Thus, a tentative DR-R cutoff ratio for a satisfactory vitamin A status in healthy American children is 0.03.

Child↗