Biomedical subjects

S A Moore

Publications and source records attributed to S A Moore.

At least 91 records · Page 5Linked to original sources

PubMed1993

Cerebral endothelium and astrocytes cooperate in supplying docosahexaenoic acid to neurons.

These findings confirm that astrocytes and cerebral endothelium, not neurons, are the cells primarily responsible for the desaturation of essential fatty acids in the brain. They suggest that cerebral endothelial cells can target omega-3 fatty acids for release from their basolateral surface and thus aid in the enrichment of omega-3 fatty acids observed in the brain. The studies further suggest that endothelium and astrocytes play an important supportive role in the brain by cooperating in the elongation and desaturation of omega-3 essential fatty acid precursors in the brain and in the transfer of DHA to neurons. In doing so, endothelium and astrocytes may contribute positively to the high level of fatty acid desaturation necessary for normal neuronal function. In composite, the present studies and previously published work support a model for supplying DHA to central nervous system neurons that could utilize either DHA or its omega-3 fatty acid precursors circulating in the blood (Figure 4). If preformed DHA were available, the cerebral endothelium would take it up and transfer it into the brain. An additional sequential pathway would utilize circulating linolenic acid or EPA. In this pathway cerebral endothelium would take up omega-3 fatty acid precursors and target them preferentially into the brain, performing some elongation and desaturation in the process. Astrocytes would subsequently complete the conversion of precursors to DHA, releasing it for uptake by neurons.

Animals↗

PubMed1993

Reproductive performance of beef heifers: effects of vulvo-vaginitis, Ureaplasma diversum and prebreeding antibiotic administration.

A group of 450 heifers, 13 to 15 mo of age, were individually identified, vaccinated (IBR, PI(3), Leptospira, Campylobacter fetus), examined (body condition score, reproductive tract evaluation, assessment of vaginal lesions), and cultured for U. diversum . Heifers were randomly allocated to either a treated group given chlortetracycline (approximately 350 mg/hd/d for 30 d in a grain crumble) or a nontreated control group. Prebreeding, most heifers showed signs of vulvovaginitis, 44% cultured positive for U. diversum . Significant associations were found between the severity of vaginal lesions and ovarian activity (P < 0.05), and between BCS and ovarian activity (P < 0.02). The U. diversum vaginal culture (positive or negative) showed no significant association with BCS, severity of vaginal lesions, or ovarian activity (all were P > 0.5). At pregnancy examination (35 d following conclusion of a 61-d breeding season), treated compared with nontreated heifers showed 1) a slight but not significant (P > 0.25) decrease in vaginal colonization by U. diversum (46 to 34% and 41 to 37%, respectively); 2) an association between increased severity of vaginal lesions and increasing pregnancy rate, especially in treated heifers; and 3) an increased pregnancy rate (72 and 57%, respectively; P < 0.01). Prebreeding treatment with chlortetracycline appeared to improve pregnancy rates in beef heifers with endemic U. diversum infections, although the role of U. diversum in heifer fertility is still not clear.

Journal Article↗

PubMed1993

Cytokine production in IgG-mediated red cell incompatibility.

The transfusion of incompatible red cells may result in fever and systemic symptoms. The mechanisms by which these symptoms are produced in the setting of antibodies that do not usually fix complement, as in the Rh system, are obscure. It has been hypothesized, on the basis of their known biologic activities, that a specific set of cytokines may be involved in such transfusion reactions. Therefore, the production of the inflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) by human monocytes in response to red cells sensitized with anti-D was investigated, as a model of IgG-dependent hemolytic transfusion reactions. IL-1 beta, IL-6, and IL-8 were detectable in the culture supernatants at 4 to 6 hours and increased up to 24 hours, whereas TNF peaked at 6 hours. Immunocytochemical stains of cell preparations demonstrated IL-1 beta, IL-8, and TNF in monocytes engaged in erythrophagocytosis. IL-8 production and phagocytosis could be inhibited by monomeric IgG, but Fab fragments of a monoclonal antibody specific for the low-affinity IgG receptor Fc gamma RII could not be, which suggests the involvement of the high-affinity receptor Fc gamma RI. Neutralizing antisera to IL-1 beta and TNF did not abrogate the production of IL-8, which suggests that sensitized red cells serve as a primary signal for this cytokine. These findings indicate that the production of inflammatory cytokines by phagocytes may be responsible for the symptomatology of IgG-mediated hemolytic transfusion reactions.

ABO Blood-Group System↗

PubMed1993

Endotoxin priming of monocytes augments Fc gamma receptor cross-linking-induced TNF-alpha and IL-1 beta release.

Cross-linking receptors for the Fc region of immunoglobulin G (IgG) (Fc gamma R) induces tumor necrosis factor-alpha (TNF-alpha) release; however, there is controversy about release of interleukin (IL)-1 beta. The purpose of this study was to investigate the role of endotoxin priming on the ability of monocytes to release these cytokines after Fc gamma R cross-linking. Monocytes were incubated with plated or soluble human IgG or albumin with or without endotoxin priming. Monocytes isolated by Percoll, containing low concentrations of endotoxin, and incubated on plated IgG released 4.5 +/- 1.6 ng/ml TNF-alpha and 1.6 +/- 0.6 ng/ml IL-1 beta. Monocytes isolated by a "clumping" technique released 1.0 +/- 0.4 ng/ml TNF-alpha but no IL-1 beta. Priming with endotoxin, which did not affect Fc gamma R expression, resulted in augmented release of TNF-alpha (4.3 +/- 1.3 vs. 0.1 +/- 0.0 ng/ml, P < 0.05) and IL-1 beta (4.0 +/- 1.0 vs. 0.6 +/- 0.3 ng/ml, P < 0.01) when clumped monocytes were incubated on plated IgG vs. plated albumin.

Cross-Linking Reagents↗

PubMed1993

Acid aspiration-induced acute lung injury causes leukocyte-dependent systemic organ injury.

The adult respiratory distress syndrome is a form of acute lung injury (ALI) that is frequently associated with systemic organ injury and often occurs in the setting of wide-spread inflammatory cell activation. However, whether conditions that lead to ALI result in systemic organ injury is unclear. This study was designed to test the hypothesis that ALI induced by acid aspiration will not result in systemic organ injury. Morphological alterations and lymph-to-plasma protein ratios were measured in autoperfused cat ileum preparations of four control animals and five animals with ALI produced by the endobronchial instillation of 0.1 N HCl (0.5 ml.kg-1.lung-1). After 2 h, the lymph-to-plasma protein ratio (a measure of microvascular permeability) was increased in the ilea of HCl-injured animals compared with control animals (0.234 +/- 0.03 vs. 0.121 +/- 0.005; P = 0.012) and was accompanied by extensive morphological alterations. Four additional HCl-injured animals were pretreated with an antileukocyte adherence antibody (anti-CD18, 2 mg/kg) that blocked the HCl-induced alterations in the ileum. This study provides evidence for significant systemic organ injury after acid aspiration-induced ALI and suggests that the neutrophil may be a key mediator.

Animals↗

PubMed1993

Taxol enhances but does not induce interleukin-1 beta and tumor necrosis factor-alpha production.

Taxol is a potent, microtubule-stabilizing, antineoplastic drug that induces interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha) release by thioglycolate-elicited mouse peritoneal macrophages. Because taxol use and subsequent cytokine release in human subjects could be associated with toxicity, the present study was performed to determine how taxol affects cytokine production from fresh human mononuclear cells. Cells were incubated overnight with varying doses of bacterial endotoxin, either with or without taxol, 10 mumol/L. Taxol alone did not induce IL-1-beta or TNF-alpha release by mononuclear cells. However, at all doses of endotoxin from 1 pg/ml to 1 microgram/ml, the addition of taxol resulted in a 50% to 100% increase in IL-1-beta release (p < 0.001) and a 25% to 50% increase in TNF-alpha release (p < 0.01). In contrast, taxol caused a reduction in intracellular pro-IL-1-beta levels. Kinetic studies demonstrated that taxol enhanced IL-1-beta release by mononuclear cells at all time points tested from 4.5 hours to 18 hours after stimulation. Taxol alone did not stimulate IL-1-beta or TNF-alpha mRNA transcription. A similar enhancement of IL-1-beta release was noted in endotoxin-stimulated alveolar macrophages. In summary, these results show that under endotoxin-free conditions, the microtubule-stabilizing agent taxol does not induce IL-1-beta or TNF-alpha production by human mononuclear cells or alveolar macrophages but does enhance production of both of these cytokines in conjunction with a second stimulus.

Blotting, Northern↗

PubMed1992

Crystallization of Photobacterium leiognathi non-fluorescent flavoprotein, an unusual flavoprotein with limited sequence identity to bacterial luciferase.

Single crystals of the non-fluorescent flavoprotein (NFP) purified from Photobacterium leiognathi strain S1 have been grown from ammonium sulphate solutions using the hanging drop vapour diffusion technique. The crystals grow as thin (0.06 mm) plates and belong to the orthorhombic space group C222(1): a = 57.06(3) A, b = 92.41(6) A, c = 99.52(6) A. There is one NFP monomer per asymmetric unit and crystals diffract to 2.2 A spacings on film. A complete native data set to 2.5 A resolution has been collected on a San Diego Multiwire Detector system at the University of Alberta and a heavy-atom derivative search is presently in progress.

Bacterial Proteins↗

PubMed1992

Undifferentiated small-cell neoplasm of the petrous apex. A case report.

We present a rare case of undifferentiated small-cell neoplasm involving the temporal bone petrous apex. The symptoms, physical examination, importance of roentgenographic findings, and pathologic findings are reviewed. While not absolutely conclusive, the collective evidence in this case supports a diagnosis of small-cell carcinoma of the lung with metastasis to the petrous apex. A discussion of temporal bone malignancies, their frequencies, and characteristics is included. To our knowledge, a review of the literature over the past 25 years reveals no other published cases of an undifferentiated small-cell carcinoma in the temporal bone.

Adult↗

PubMed1992

Intracranial dissemination of an ACTH secreting pituitary neoplasm--a case report and review of the literature.

A 52-year-old woman developed recurrent hypercortisolism 3 yr after successful surgical treatment of Cushing's disease. At postmortem, eosinophilic pituitary tissue showing positive ACTH immunohistochemical staining was present in the frontal lobe and cerebellum but there was no tumor in the sella. In the absence of a pituitary tumor, extrasellar ACTH producing tissue could arise from seeding of the cerebrospinal fluid with tumor cells at the time of operation or from an atypical pituitary carcinoma. In this report we review the mechanisms of intracranial dissemination of pituitary tissue and ACTH-secreting pituitary carcinomas, including parasellar invasion, meningeal seeding, and cerebrospinal and hematogenous spread.

Adenoma↗

PubMed1992

Vascular smooth muscle hyperplasia underlies the formation of glomeruloid vascular structures of glioblastoma multiforme.

The origin of the vascular hyperplasia seen in glioblastoma multiforme is a matter of debate. To test the predominant hypothesis that these glomeruloid structures are of endothelial origin the following study was undertaken. Seven glioblastomas containing prominent glomeruloid vascular structures were stained with Ulex europaeus agglutinin I (UEA-1) and with antibodies against factor VIII/related antigen (fVIII/RAg), glial fibrillary acidic protein (GFAP), S-100 protein, muscle specific alpha-actin (MSA) and smooth muscle specific alpha-actin (SMSA). The GFAP and S-100 antibodies stained the neoplastic glial component of each tumor but did not bind to vascular cells. Endothelial cells lining the lumina of normal vessels and the lumina of glomeruloid vascular structures stained positively with both UEA-1 and fVIII/RAg antibody. No other cells were found to be stained by UEA-1 or by fVIII/RAg antibody. Smooth muscle cells of the normal vasculature stained positively exclusively with anti-MSA and anti-SMSA antibodies. The same pattern of positive actin antibody staining was seen in the majority of cells forming the glomeruloid structures; however, the cells lining the vascular lumina did not bind the MSA and SMSA antibodies. These data strongly suggest that the vascular proliferation resulting in glomeruloid structures is due in large measure to smooth muscle hyperplasia.

Actins↗

PubMed1992

Smooth muscle can comprise the sarcomatous component of gliosarcomas.

The sarcomatous component of gliosarcomas is thought by many to originate from the vascular proliferation seen in glioblastoma multiforme and has, therefore, been assumed to be endothelial. Immunohistochemical staining of four gliosarcomas has led us to an alternate theory. Pathologically all four tumors were composed of at least two cell types; the first had a stellate, glial appearance and the second was either spindled or polygonal in shape. Polygonal cells were associated with glomeruloid vascular structures in some areas. Both components of each neoplasm were cytologically malignant. Glial fibrillary acidic protein and S-100 antibodies stained most of the glial-appearing cells and some of the spindled cells, but not the polygonal cells. Muscle specific alpha-actin and smooth muscle specific alpha-actin antibodies stained only the malignant spindled and polygonal cells and normal vascular smooth muscle. Ulex europaeus agglutinin I and anti-factor VIII/related antigen antibody stained only cells lining vascular lumina. The staining results suggest that the malignant mesenchymal component of these tumors is of smooth muscle origin. Having demonstrated elsewhere that glomeruloid vascular structures of glioblastoma multiforme contain smooth muscle cells, we propose here that gliosarcomas can represent one end of the spectrum of glioma-induced vascular smooth muscle proliferation.

Actins↗

PubMed1992

Differential metabolism of hydroxyeicosatetraenoic acid isomers by mouse cerebromicrovascular endothelium.

Hydroxyeicosatetraenoic acid (HETE) derivatives of arachidonic acid are produced in the brain and have been implicated as pathologic mediators in various types of brain injury. To understand better their fate in the brain, particularly in cerebral microvessels, several HETEs were incubated with cultured mouse cerebromicrovascular endothelium for 1, 2, and 4 h, followed by HPLC analysis of medium and cellular lipids. 5(S)-, 8(RS)-, and 9(RS)-HETE were not metabolized by the cells, but were extensively incorporated, unmodified, into cell lipids. On the other hand, 11(RS)-, 12(S)-, and 15(S)-HETE were extensively metabolized and only minimally incorporated into cell lipids. Previously, the major 12-HETE metabolite was identified as 8-hydroxyhexadecatrienoic acid. In the present study, we identified the major 11-HETE metabolite as 7-hydroxyhexadecatrienoic acid and the major 15-HETE metabolite as 11-hydroxyhexadecatrienoic acid. omega-3 compounds, 15(S)- and 12(S)-hydroxyeicosapentaenoic acids (HEPE), were also metabolized to more polar compounds, but to a lesser extent than their tetraenoic acid, omega-6 counterparts. Comparison of 5-, 12-, and 15-HETE enantiomers revealed no differences in metabolism or incorporation between the R and S stereoisomers. These data suggest that many isomers of HETE and HEPE can be incorporated into cell lipids or metabolized by pathways that do not distinguish between enantiomers. These pathways, however, are sensitive to the position or number of double bonds and are selective based on the position of the hydroxyl group.

Animals↗

PubMed1992

Receptor-linked hydrolysis of phosphoinositides and production of prostacyclin in cerebral endothelial cells.

The receptor agonist-mediated hydrolysis of phosphoinositides and production of prostacyclin were studied in murine cerebral endothelial cells (MCEC). Of 11 neurotransmitters and neuromodulators examined, carbachol, noradrenaline (NE), bradykinin, and thrombin significantly increased 3H-inositol phosphate accumulation in the presence of LiCl (20 mM). The maximal stimulation of [3H]inositol monophosphate ([3H]IP1) reached approximately 11, 11, seven, and four times the basal levels for carbachol, NE, bradykinin, and thrombin, respectively. The EC50 values of IP1 accumulation for carbachol and NE were 34 and 0.16 microM, respectively. The muscarinic antagonists, atropine and pirenzepine, blocked the carbachol-induced IP1 accumulation with Ki values of 0.3 and 30 nM, respectively. The adrenergic antagonist, prazosin, blocked NE-induced IP1 accumulation with a Ki of 0.1 nM. The calcium ionophore A23187, histamine, glutamate, vasopressin, serotonin, platelet activating factor, and substance P did not stimulate IP1 accumulation. A23187, bradykinin, and thrombin stimulated prostacyclin release to approximately four, four, and two times the basal levels, respectively, whereas carbachol and NE had little effect upon prostacyclin release. These results suggest that the activation of phospholipase C and of phospholipase A2 in MCEC are regulated separately.

Animals↗

PubMed1992

Expression and regulation of human alveolar macrophage-derived interleukin-1 receptor antagonist.

The alveolar macrophage (AM) is the sentinel immune cell of the distal airspace of the lung. These mononuclear phagocytic cells represent the major host defense against inhaled environmental agents. When activated, the AM has the capacity to release reactive oxygen and arachidonic acid metabolites and produce a number of cytokines, such as interleukin-1 (IL-1). This latter cytokine has pleiotropic effects on a variety of cells and has been implicated as one of the preeminent mediators of acute inflammation. Recently, an IL-1 receptor antagonist (IRAP) has been isolated, purified, and cloned from peripheral blood monocytes (PBM) stimulated with either adherent IgG (adhIgG) lipopolysaccharide (LPS), or phorbol myristate acetate. IRAP acts as a true receptor antagonist without agonist activity. We postulated that the AM would be a significant cellular source of IRAP from the lung. To test this hypothesis, normal human AM were immediately isolated or stimulated in a dose-dependent fashion with either LPS or adhIgG. For comparison, PBM were also isolated and treated in a similar manner. PBM expressed steady-state IRAP mRNA by Northern blot analysis only in response to LPS or adhIgG. In contrast, AM were found to express significant levels of antigenic IRAP by Western blot analysis, immunostaining, and specific ELISA, and express steady-state levels of IRAP mRNA under unstimulated culture conditions. Moreover, LPS or adhIgG failed to induce AM-derived IRAP antigen generation over unstimulated control.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗

PubMed1992

Ganglioglioma: 13 years of experience.

A 13-year retrospective review of 17 patients with gangliogliomas treated at the University of Iowa was conducted to investigate the association between tumor location, extent of resection, pathological findings, and patient prognosis. Thirteen were in the cerebral hemispheres and 4 in the midline. The mean ages at diagnosis and symptom onset were 16 and 8.8 years, respectively. The most common presenting symptom was seizures (11 patients); focal neurological deficit was seen in 5 patients and headache in 1. Patients with hemispheric tumors had an older age at time of diagnosis and a longer duration of symptoms. Pathologically, they had more microcalcifications, lymphocytic infiltration, microcystic degeneration, and eosinophilic bodies. Cerebral hemispheric tumors were more amenable to total resection than midline neoplasms, 77% versus 25%, respectively. In the patients with hemispheric tumors, 10 patients were tumor-free after total resection. Two of the 3 patients with partial resection had stable residual tumors. The third died of tumor progression. In the 4 patients with midline neoplasms, one was tumor-free after total resection. The other 3 had subtotal resection and radiation therapy. Two died within 2 years; the third is still alive with progressive tumor. Five of 9 patients who had seizure disorders and who underwent total tumor removal were seizure-free postoperatively. The other 4 patients and the 2 with partial surgical resection continued to have seizures.

Adolescent↗

PubMed1992

A sensitive ELISA for the detection of human monocyte chemoattractant protein-1 (MCP-1).

The recruitment of monocytes into tissue is associated with both acute and chronic inflammation. Although monocyte migration is measured in vitro by monocyte chemotaxis, this technique is often difficult to determine the specific quantitative contribution of a monocyte chemotaxin. We have developed a sensitive sandwich ELISA for the detection of monocyte chemoattractant protein-1 (MCP-1), a highly specific monocyte activating/chemotactic peptide. Polyclonal antibodies were generated from rabbits. The IgG fraction of the antiserum was isolated by a protein A column, with a portion of the antibodies biotinylated. Avidin-conjugated horse radish peroxidase was used for enzymatic, colorimetric analysis. The lower threshold for detection of MCP-1 was 50 pg/ml, and the ELISA was specific for MCP-1, since it failed to recognize other cytokines in a dose-dependent fashion. Furthermore, this ELISA had the capacity to measure endothelial cell and pulmonary fibroblast-derived MCP-1. The development of a sensitive ELISA for the detection MCP-1 is significant, since it will allow the measurement MCP-1 from biologically relevant fluids, and aid in establishing whether MCP-1 is present in disease.

Animals↗

PubMed1992

Brain microvascular smooth muscle and endothelial cells produce granulocyte macrophage colony-stimulating factor and support colony formation of granulocyte-macrophage-like cells.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent stimulator of macrophages and neutrophils and plays a role in inflammatory diseases. In this article, we report that mouse brain-derived microvascular smooth muscle cells (SM) and endothelial cells (En) in coculture with splenocytes support the colony proliferation of immature granulocyte-macrophage-like (GM) cells. Unstimulated SM and En cells release GM-CSF as shown by ELISA assay and SM expresses mRNA for GM-CSF by polymerase chain reaction (PCR). Stimulation of SM and En by a nonspecific activator (lipopolysaccharide) results in upregulation of GM-CSF production. GM colonies cannot be grown on cultured astrocytes or on extracellular matrix alone prepared from smooth muscle or endothelium. However, colonies form on the extracellular matrix and on astrocytes, either in the presence of SM- or En-conditioned medium or after the addition of recombinant GM-CSF. The GM cells are positive for nonspecific esterase, peroxidase, and MAC-1 markers but are negative for FC gamma receptors and for Thy 1.2, CD8, CD4, MHC class II, and Asialo GM1 markers. These observations emphasize the possibility for active participation of brain microvasculature SM and En in acute inflammatory reactions of the central nervous system.

Amino Acid Sequence↗

PubMed1991

Acute and chronic exposure of mouse cerebral microvessel endothelial cells to increased concentrations of glucose and galactose: effect on myo-inositol metabolism, PGE2 synthesis, and Na+/K(+)-ATPase transport activity.

Cultured mouse cerebral microvessel endothelial cells have a large intracellular myo-inositol content and rapidly take up extracellular myo-inositol. Myo-inositol uptake occurs by a high- and low-affinity transport system. Both transport systems appear to be Na(+)-dependent. The high- and low-affinity transport systems have a Km of 11 and 198 mumol/L and a Vmax of 47 and 381 pmol/min/mg protein, respectively. Acute exposure of cultured cells to 30 mmol/L D-glucose or D-galactose causes a decrease in myo-inositol uptake. The acute effect of glucose and galactose on myo-inositol uptake is sensitive to the extracellular myo-inositol concentration. The acute effect of glucose is apparently due to a competitive inhibition of high-affinity myo-inositol transport and has a Ki of 21 mmol/L. L-Glucose is more effective than D-glucose in decreasing myo-inositol uptake. In contrast, 2-deoxyglucose or 3-0-methylglucose does not acutely inhibit myo-inositol uptake. This suggests that the hydroxyl groups on carbons 2 and 3 of glucose are necessary for inhibitory activity. Chronic exposure of cells to media containing 136.4 mumol/L myo-inositol and 30 mmol/L glucose has no effect on myo-inositol accumulation from the extracellular fluid, myo-inositol incorporation into inositol phospholipids, or total myo-inositol content. Chronic exposure of the cells to media containing 30 mmol/L glucose causes only a small increase in the intracellular sorbitol content. In contrast, chronic exposure of the cells to media containing 30 mmol/L galactose causes a large increase in galactitol content and a decrease in myo-inositol accumulation, myo-inositol incorporation into inositol phospholipids, and intracellular myo-inositol content. Sorbinil treatment of the galactose-supplemented media protects the cells form changes in myo-inositol metabolism and content. Chronic exposure of the cells to media containing 30 mmol/L glucose or 30 mmol/L galactose causes a decrease in ouabain-sensitive Na+/K(+)-ATPase transport activity, which is corrected by the addition of sorbinil to the media. Chronic exposure of the cells to media containing 45 mmol/L glucose, but not galactose, causes an increase in PGE2 production. These studies suggest that acute or chronic exposure of cultured microvessel endothelial cells to increased concentrations of glucose or galactose causes a decrease in myo-inositol uptake by different mechanisms. Chronic exposure of the cells to increased concentrations of glucose or galactose causes alterations in endothelial cell properties, including Na+/K(+)-ATPase transport activity and eicosanoid synthesis. The data are not clearly supportive of polyol accumulation and myo-inositol depletion as being responsible for the decrease in Na+/K+ pump activity.

Animals↗