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Biomedical subjects

J A Mitchell

Publications and source records attributed to J A Mitchell.

At least 181 records · Page 10Linked to original sources
PubMed1991

Characterization of nitric oxide synthases in non-adrenergic non-cholinergic nerve containing tissue from the rat anococcygeus muscle.

Tissue homogenates prepared from rat anococcygeus muscle converted L-arginine to L-citrulline indicating the presence of nitric oxide (NO) synthase. NO synthase activity was also found in crude and partially-purified soluble and particulate fractions prepared from the homogenates. Both soluble and particulate NO synthase were dependent on NADPH, 5,6,7,8-tetrahydrobiopterin and calcium, and inhibited by NG-nitro-L-arginine. Tissue homogenates or crude cytosolic and membrane fractions from rat vas deferens, which does not contain NO releasing non-adrenergic non-cholinergic neurones, had no NO synthase activity.

Amino Acid Oxidoreductases↗
PubMed1991

Divergence of muscle and liver fructose 2,6-diphosphate in fasted exercising rats.

Previous studies demonstrate that nonexercising muscle may serve as a source of lactate for hepatic gluconeogenesis during long-term exercise. The concentration of fructose 2,6-diphosphate (F-2,6-P2), a signal molecule that accelerates glycolysis, was examined in liver and muscles of fed and fasted resting rats and in fasted rats run for 5, 15, or 30 min at 21 m/min (15% grade). Liver F-2,6-P2 decreased in response to fasting and exercise. White quadriceps (composed predominantly of type IIb fibers) F-2,6-P2 increased from 2.2 +/- 0.1 to 4.5 +/- 0.4 pmol/mg in the fasted rats in response to 30 min of treadmill running. No increase was observed in the red region of the quadriceps (composed of type IIa fibers). The fasted rats also exhibited a threefold increase in glucose 1,6-diphosphate (G-1,6-P2) in the white quadriceps after 30 min of exercise, whereas no significant changes were observed in the red quadriceps or in liver. The increases in F-2,6-P2 and G-1,6-P2 may be important in accelerating glycolysis and enhancing lactate production in muscles that are not glycogen depleted during long-term exercise.

Animals↗
PubMed1991

Retrieval from full-text medical literature: the dream & the reality.

While the retrieval of the full-text of a document might seem to end all the hassle of using traditional retrieval systems, the results of the MEDLINE/Full-Text Project indicate that retrieval from the current full-text databases of biomedical journal literature does not match the dream. During the first phase of the project the researchers learned that searching the full-text databases resulted in the retrieval of a significantly larger number of relevant documents than MEDLINE. However, the full-text databases also resulted in a large number of non-relevant documents. Currently the researchers are focusing on how to search these databases to continue retrieving the large number of relevant documents but without so many non-relevant items.

Databases, Bibliographic↗
PubMed1991

The creation and early implementation of a high speed fiber optic network for a university health sciences center.

In late 1989 the University of Missouri Health Sciences Center began the process of creating an extensive fiber optic network throughout its facilities, with the intent to provide networked computer access to anyone in the Center desiring such access, regardless of geographic location or organizational affiliation. A committee representing all disciplines within the Center produced and, in conjunction with independent consultants, approved a comprehensive design for the network. Installation of network backbone components commenced in the second half of 1990 and was completed in early 1991. As the network entered its initial phases of operation, the first realities of this important new resource began to manifest themselves as enhanced functional capacity in the Health Sciences Center. This paper describes the development of the network, with emphasis on its design criteria, installation, early operation, and management. Also included are discussions on its organizational impact and its evolving significance as a medical community resource.

Academic Medical Centers↗
PubMed1991

Use of a microcomputer database system in a statewide effort for data collection in medical genetics.

The Genetics Office Automation System (GOAS) is a database management system for the collection and reporting of medical genetics data. We have previously reported on its implementation in a single university center [1,2]. We report here on its implementation in a coordinated data collection effort for the State of Missouri. We discuss the current status of the data collection activities and procedures to share data collected at an individual center with state, regional, and national data collection efforts.

Data Collection↗
PubMed1991

Using medical genetics applications to educate for computer competence.

This article proposes specific areas of computing competence and illustrates how these skills can be acquired as an integral part of the curriculum of medical genetics. Geneticists are at the forefront in the use of computers for medical care, because of the driving force of the Human Genome Project. Computer searching of international data bases is the most efficient method to keep current with the explosion in molecular genetics data and with its immediate relevance to clinical care. The use of computers in genetics education could go far beyond the use of computer-assisted instruction (CAI) to show how to use computer systems to assist with clinical decisions. The proposed basic computer skills can be obtained using genetics software. The six proposed skills include the use of (1) microcomputers, (2) productivity software, (3) CAI, patient simulations and specific application programs, (4) remote computers, (5) data bases and knowledge bases, and (6) computers to improve the clinical care of patients.

Clinical Medicine↗
PubMed1990

L-glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta.

The present study investigates the effect of the amino acid L-glutamine (L-Gln) on the release of endothelium-derived relaxing factor (EDRF) from the luminally perfused rabbit aorta and on endothelium-dependent relaxations of rabbit aortic strips. L-Gln (200 microM) had no effect on the acetylcholine (Ach)-induced release of EDRF from freshly prepared aortic tissues. The concentration of L-arginine (L-Arg) in endothelial cells isolated from these aortae was approximately 4 mM, as determined by HPLC analysis. After an initial equilibration period of 2 h and two consecutive infusions of Ach (55 microM for 15 min) at 2 and 3 h, L-Arg levels fell by 62 +/- 14% (n = 4). Under these conditions, L-Gln (200 microM) but not D-Gln (200 microM) inhibited the release of EDRF by 50 +/- 4% (n = 7). This effect of L-Gln was partially reversed by infusions of L-Arg (500 microM) but not D-Arg (500 microM). L-Gln (200 microM) but not D-Gln (200 microM) potentiated the inhibitory effect of N omega-nitro-L-arginine (30 microM), an inhibitor of EDRF biosynthesis, on Ach-induced relaxations of rabbit aortic strips, whereas L-Gln alone had no effect. Thus, L-Gln inhibits the release of EDRF from intact blood vessels presumably by interfering with the generation of L-Arg by the endothelium.

Acetylcholine↗
PubMed1990

Cultured endothelial cells maintain their L-arginine level despite the continuous release of EDRF.

Endothelial cells cultured from bovine aorta and grown on microcarrier beads contain 107 +/- 9 microM L-arginine (Arg; n = 11). When packed into a jacketed chromatography column and perfused with Krebs solution, the cells showed a substantial and sustained release of endothelium-derived relaxing factor (EDRF) for up to 2 h, which was further enhanced by infusions of adenosine diphosphate (4 microM). In contrast to other amino acids, such as L-alanine, L-aspartate, L-glutamine, L-glutamate or L-serine, which showed a time-dependent decrease to less than 30% of their original level within 2 h, Arg remained at control levels for 30 min and decreased only by 25% after 2 h. Thus endothelial cells can generate Arg from an intracellular source to maintain their Arg level despite the continuous formation of EDRF.

Amino Acids↗
PubMed1990

Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine.

NG-monomethyl-L-arginine (MeArg) inhibits the release of endothelium-derived relaxing factor (EDRF) from endothelial cells (EC) and the formation of nitric oxide (NO) from L-arginine (Arg) in EC and activated macrophages. We have compared the inhibitory potency of MeArg to that of N omega-nitro-L-arginine (NO2Arg), a more potent inhibitor of EDRF synthesis in vitro. NO2Arg (100 microM) was significantly more potent than MeArg in inhibiting the endothelium-dependent relaxation of rabbit aorta induced by acetylcholine. MeArg and NO2Arg (10 and 30 microM) also inhibited the release of EDRF from bovine aortic cultured EC. In the anaesthetized rat in vivo, the pressor effect of NO2Arg (3 and 10 mg kg-1) was significantly larger and longer lasting than that of MeArg. These differences in potency could be due to the extensive metabolism of MeArg but not NO2Arg to L-citrulline (Cit) and subsequently to Arg by EC. The enzyme responsible for the conversion of MeArg to Cit had the characteristics of a novel deiminase, NG,NG-dimethylarginine dimethylaminohydrolase, recently isolated from rat kidney.

Acetylcholine↗
PubMed1990

Alterations in intrauterine oxygen tension during the estrous cycle in the rat and hamster and its regulation by ovarian steroid hormones: a comparative study.

The results indicate that marked fluctuations in oxygen availability occur during the estrous cycle in both rats and hamsters. Patterns of luminal pO2 were similar in that levels were intermediate during metestrus and maximal during diestrus. By contrast, minimal pO2 levels occurred during estrus in the rat vs. during proestrus in the hamster. The species also differed in the range of mean pO2 occurring during the cycle: approximately 5-50 mmHg in the hamster vs. 25-50 mmHg in the rat. Ovariectomy results in marked increases in luminal pO2 in both species. The increase is reduced by hormone replacement.

Animals↗
PubMed1990

The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of L-arginine by cultured endothelial cells.

The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived relaxing factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-citrulline (L-Cit), L-Cit-L-Phe, and NG-monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[14C]Cit to L-[14C]Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor.

Animals↗
PubMed1990

Inhibition by L-glutamine of the release of endothelium-derived relaxing factor from cultured endothelial cells.

L-Glutamine (0.02-2 mM) but not D-glutamine (0.2 mM and 2 mM) inhibited the release of endothelium-derived relaxing factor (EDRF) from bovine aortic endothelial cells cultured in the presence or absence of L-arginine. Inhibition was maximal at a concentration of 200 microns, and was reversed by L-arginine (50 microns) but not D-arginine (100 microns). L-Glutamic acid (2 mM) or ammonium chloride (1 mM), putative products of the metabolism of L-glutamine in endothelial cells, had no effect on EDRF release. L-Glutamine (0.2 mM and 2 mM) but not D-glutamine (2 mM), L-glutamic acid (2 mM) or ammonium chloride (1 mM) also inhibited the generation of L-arginine in endothelial cells. Thus, L-glutamine inhibits EDRF release by preventing the generation of L-arginine.

Animals↗
PubMed1990

Correlation between lymphocyte proliferative responses and dendritic cell migration in regional lymph nodes following skin painting with contact-sensitizing agents.

We have investigated whether there exists a correlation between the induction of draining lymph node cell (LNC) proliferation in contact allergy and the accumulation of dendritic cells (DC) within such lymph nodes. CBA/Ca mice, which compared with mice of BALB/c strain, mount a more vigorous lymphocyte proliferative response following sensitization, also exhibited a more marked accumulation of DC in draining lymph nodes 24 h following skin painting. Moreover, studies with the skin-sensitizing fluorochromes fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC) revealed that DC-enriched fractions of draining LNC prepared from CBA/Ca mice contained a higher percentage of antigen-bearing cells than did those from BALB/c mice. A relationship between DC migration into lymph nodes and the magnitude of the induced LNC proliferative response was also indicated by experiments performed in BALB/c mice with a variety of contact allergens. It was observed that there was a direct correlation between the vigour of the proliferative response measured 3 days following exposure and the frequency of DC in draining nodes at 24 h. Collectively these data suggest that following skin sensitization the migration of DC into the draining lymph nodes influences quantitatively the primary immune response and the development of contact allergy.

Allergens↗
PubMed1990

Antigenic competition in contact sensitivity. Evidence for changes in dendritic cell migration and antigen handling.

The frequency and antigen-bearing characteristics of dendritic cells (DC) within draining lymph nodes have been examined during antigenic competition in contact sensitivity. Pre-exposure of mice to oxazolone on the flank resulted in a marked depression of subsequent fluorescein isothiocyanate (FITC)-induced lymph node cell (LNC) proliferation. Antigenic competition was associated with an increased frequency of DC in the draining lymph nodes, but also with a reduced amount of antigen per cell. Thus, at 24 hr the draining nodes of FITC-challenged mice previously exposed to oxazolone exhibited an increased number of DC compared with control animals. Flow cytometric analysis revealed, however, that the percentage of antigen-bearing DC was reduced and that the median amount of antigen borne by DC was lower. Since exposure to oxazolone caused a significant increase in the frequency of DC in distant nodes, the changes observed in antigenic competition may, at least in part, be attributable to systemic effects on DC migration following application of the first antigen. These data indicate that the reduced primary proliferative response which characterizes antigenic competition in contact sensitivity is associated with, and may result from, induced changes in dendritic cell behaviour.

Animals↗
PubMed1989

Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2.

Complement receptor type 2 (CR2;CD21), a member of the superfamily of proteins containing short consensus repeats (SCRs), is the B cell receptor for both the gp350/220 envelope protein of Epstein-Barr virus (EBV), and for the C3dg protein of complement. By analysis of CR2 deletion mutants and chimeras formed with CR1 (CD35) we determined that of the 15 SCRs in CR2, the NH2-terminal two SCRs are necessary and sufficient to bind both gp350/220 and C3dg with affinities equivalent to those of the wild-type receptor. The epitope for OKB-7, a mAb that blocks binding of both EBV and C3dg and shares with these ligands B cell-activating capabilities, also requires both SCR-1 and SCR-2, whereas mAbs lacking these functions bind to other SCRs. Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function.

Animals↗
PubMed1989

Innervation of the pituitary gland by supraependymal neurons.

Retrograde transport of horseradish peroxidase (HRP) was used to identify supraependymal neurons projecting to the pituitary gland in the hamster. Supraependymal neurons overlying the median eminence were labeled by HRP injections into the neural and intermediate lobes of the pituitary gland; no neurons were labeled following HRP injections confined to the anterior lobe. Supraependymal neurons innervating the pituitary gland may provide a means whereby cerebrospinal fluid-borne substances modulate neuro-intermediate lobe function.

Animals↗