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S A Moore

Publications and source records attributed to S A Moore.

At least 73 records · Page 4Linked to original sources
PubMed1995

Structural refinement of the non-fluorescent flavoprotein from Photobacterium leiognathi at 1.60 A resolution.

The crystallographically-determined structure of the non-fluorescent flavoprotein (NFP) from Photobacterium leiognathi, a homolog of the bacterial luciferase subunits, has been refined to a conventional R-factor [formula: see text] of 0.175 using synchrotron data between 10.0 and 1.60 A resolution. The molecular structure is a homodimer of beta/alpha domains, the monomer having structural similarities to (beta alpha)8 barrel proteins. However, one beta-strand and three alpha-helices of a typical (beta alpha)8 domain are not present in the NFP structure. The refined structure of NFP consists of the 228 amino acid polypeptide, 191 water molecules, a sulfate ion, and two flavin mononucleotides (FMNs) each with a covalently-attached myristate (C14 fatty acid). Both flavin adducts are well-ordered and have exceptional electron density for both the FMN and the myristate moieties. Each flavin mononucleotide-myristate adduct is characterized by a stereospecific linkage (the S enantiomer) between C-6 of the flavin isoalloxazine ring and the C-3' atom of the fatty acyl chain. The stereospecific nature of this flavin-fatty acid linkage suggests that it is the result of an enzyme-catalyzed reaction, most likely the bioluminescence reaction itself. The myristate chains are buried from solvent in hydrophobic pockets in the interior of the protein. Four amino acid side-chains of the NFP polypeptide have been modeled with alternate conformations. Five of the protein's seven alpha-helices have classical C-capping boxes. NFP is dimeric and many of the extensive contacts at the dimer interface are mediated by hydrogen-bonded water molecules as well as by hydrophobic interactions. One of the myristate acyl chains sits between NFP monomers and contributes a significant portion of the hydrophobic interactions at the NFP dimer interface.

Crystallography↗
PubMed1995

Taxol and colchicine increase LPS-induced pro-IL-1 beta production, but do not increase IL-1 beta secretion. A role for microtubules in the regulation of IL-1 beta production.

IL-1 beta is a proinflammatory cytokine secreted chiefly by monocytes and macrophages. Currently, much of its mechanism of processing and secretion is poorly understood, but there is increasing evidence that the microtubule system may be involved. For example, it is known that taxol and colchicine, two drugs that affect microtubule structure and function, increase LPS-induced IL-1 beta release. However, it is not known whether these drugs affect the synthesis of the 31-kDa precursor (pro-IL-1 beta) or the processing and release of mature IL-1 beta. To test this, an assay was used that allowed for the temporal separation of IL-1 beta synthesis and release. The addition of taxol or colchicine to the secretory phase of the assay resulted in no significant change in IL-1 beta release. However, when these drugs were added to the stimulus for IL-1 beta production, there was a significant increase in both IL-1 beta release and total IL-1 beta production, as measured by ELISA. These findings indicate that taxol and colchicine increase LPS-induced IL-1 beta release by an increase in the production of the precursor molecule. Thus, it is unlikely that microtubules are involved in the IL-1 beta secretory machinery in any significant manner, but they do play a role in the regulation of pro-IL-1 beta production.

Animals↗
PubMed1995

Crystal and molecular structures of human progastricsin at 1.62 A resolution.

The crystal and molecular structures of human progastricsin (hPGC) have been determined using multiple isomorphous replacement methods and anomalous scattering in conjunction with a phased translation function. The structure has been refined to a conventional R-factor (= sigma parallel Fo magnitude of - magnitude of Fc parallel / sigma magnitude of Fo magnitude of) of 0.179 with data to 1.62 A resolution. The first 37 amino acid residues of the prosegment are similar in conformation to the equivalent residues of porcine pepsinogen (pPGN). As in pPGN, the N zeta atom of Lys37p sits between the active-site carboxylate groups of Asp32 and Asp217, thereby preventing catalysis. The side-chains of Tyr38p and Tyr9 sit in the S1' and S1 substrate-binding pockets of hPGC, respectively, in an analogous manner to what is observed in porcine pepsinogen. There are large conformational differences centered around the region containing residues Arg39p to Pro6, relative to the equivalent region in the structure of pPGN. Two surface loops in the vicinity of this segment are also displaced relative to those in pPGN and in mature aspartic proteinases (Phe71 to Thr81 (the "flap"), and Tyr125 to Thr131). In hPGC, Tyr75 O eta does not make its usual hydrogen bond to Trp39 N epsilon 1. Rather, the "flap" containing Tyr75 is excluded from the active site by the polypeptide segment Arg39p to Pro6. However, the conformation of the inhibitory segment, Lys37p to Tyr38p, is virtually identical with that observed in pPGN. Hence the structures of these two proteins indicate that aspartic proteinase zymogens keep themselves inactive at neutral pH by a very similar mechanism in human progastricsin and porcine pepsinogen. This similarity likely carries over to all members of both the pepsinogen A and C families of aspartic proteinase zymogens.

Amino Acid Sequence↗
PubMed1995

The expression of heat shock protein 70 decreases with age in lymphocytes from rats and rhesus monkeys.

The ability of cells to express heat shock proteins in response to a stress such as heat is universal to all organisms and is believed to play a critical protective role. Therefore, it was of interest to determine the influence of aging on the ability of lymphocytes to express the heat shock protein hsp70 in response to a heat shock (42.5 degrees C for 1 h). Splenic lymphocytes isolated from old (24-26 months) rats showed a marked decrease in the induction of hsp70 protein levels or hsp70 synthesis when compared to lymphocytes isolated from young (4-5 months) rats. An age-related decrease in the induction of hsp70 levels by heat also was observed in peripheral lymphocytes isolated from rhesus monkeys. The decline with age in the induction of hsp70 by lymphocytes from rats was paralleled by a decrease in the induction of hsp70 mRNA and the nuclear transcription of hsp70. In addition, it was found that the ability of extracts from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased approximately 50% with age. Therefore, it appears that the reduced ability of lymphocytes from old rats to express hsp70 in response to a heat shock occurs at the level of transcription because of an alteration in the ability of the heat shock transcription factor to bind the HSE on the promoter of the hsp70 gene. The age-related decrease in the induction of hsp70 appears to be physiologically important because the viability of spleen lymphocytes exposed to high temperatures decreases significantly with age.

Aging↗
PubMed1995

Primary germinoma of the spinal cord: a case report with 28-year follow-up and review of the literature.

Germ cell neoplasms occur in extra-gonadal midline locations of the retroperitoneum, mediastinum, pineal gland, areas of the suprasellar cistern, and rarely in the spinal cord. We recently reviewed a case of an unresectable lumbar spinal cord tumor in a 16-year-old female previously diagnosed as "metastatic poorly differentiated carcinoma." An extensive evaluation for a primary neoplasm at that time was unsuccessful and the patient was treated with local radiation therapy. Recently, additional histochemical and immunocytochemical studies were performed on the archival formalin-fixed paraffin-embedded material and the clinical history was reviewed. These ancillary studies (including positive immunohistochemical staining for placental alkaline phosphatase) support a diagnosis of intramedullary germinoma of the conus medullaris. This patient has enjoyed 28 years of disease free survival which reflects the radiosensitive nature of this neoplasm. These data lend support to the existence of a primary germinoma in the spinal cord and illustrate the utility of using histochemical stains and immunohistochemistry to assist in diagnosing this treatable neoplasm.

Adolescent↗
PubMed1995

Arginine vasopressin stimulates protein synthesis but not proliferation of cultured vascular endothelial cells.

We previously showed that rat and cow blood vessels contain arginine vasopressin (AVP) of local origin. In the present study, to investigate potential roles for this locally produced peptide, we examined the effects of AVP on growth of cultured vascular endothelial and smooth muscle cells (EC, SMC). Treatment of cultured bovine aortic endothelial (BAE), murine cerebral microvascular endothelial (MME), or murine cerebral microvascular smooth muscle (MMSM) cells with AVP produced dose-dependent increases in total protein content with maximum increases of 11, 46, and 33% over vehicle-treated controls, respectively. AVP also dose-dependently increased new protein synthesis, as reflected by [3H]leucine incorporation into BAE and MME cell protein, with maximal increases of 34 and 24%, respectively. In addition, the AVP-stimulated increase in protein synthesis could be significantly attenuated in both BAE and MME cells by simultaneous addition of a specific AVP V1 receptor antagonist. In contrast, AVP did not affect total cell number or DNA synthesis, as reflected by [3H]thymidine incorporation, in any cell type. Neither was cell size, as measured by forward light scatter with a fluorescence-activated cell sorter (FACS), changed by treatment with AVP. However, the density of individual cells, as measured by orthogonal light scatter with FACS, was increased by AVP. These data demonstrate that AVP stimulates protein synthesis but not proliferation of cultured vascular EC and SMC and suggest that locally produced AVP may function as a growth factor for these cells.

Animals↗
PubMed1995

Cervical epidural hematoma secondary to an extradural vascular malformation in an infant: case report.

We present a report of a 22-month-old infant with a spontaneous spinal epidural hematoma arising from a purely epidural vascular malformation. Although often suspected as a cause of spontaneous epidural hemorrhage, vascular malformations have rarely been demonstrated. The important aspects of the presenting symptoms in this young age group are highlighted. We discuss the entity of spontaneous epidural hemorrhage and the characteristics that distinguish purely epidural from dural arteriovenous malformations.

Arteriovenous Malformations↗
PubMed1995

Immunosuppressive properties of surfactant and plasma on alveolar macrophages.

Alveolar macrophages have been shown to be major producers of the potent proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha, and of the antiinflammatory cytokine interleukin-1 receptor antagonist. During the adult respiratory distress syndrome the normally surfactant-coated alveolus becomes flooded with plasma proteins, altering the milieu of alveolar cells such as alveolar macrophages. To understand alveolar macrophage function during the adult respiratory distress syndrome, the individual and combined effects of surfactant and plasma on alveolar macrophage cytokine production was examined. A synthetic surfactant (Exosurf) and a bovine-derived surfactant (Survanta) both inhibited production of interleukin-1 beta, pro-interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist in a dose-dependent manner. This inhibition was noted when both endotoxin and heat-killed Staphylococcus aureus were used as stimuli. Autologous plasma also inhibited interleukin-1 beta and tumor necrosis factor-alpha release in a dose-dependent manner, but, unlike surfactant, plasma did not inhibit interleukin-1 receptor antagonist release. Similarly, the combination of plasma and surfactant inhibited interleukin-1 beta and tumor necrosis factor-alpha release but not interleukin-1 receptor antagonist release. In support of these data, interleukin-1 receptor antagonist was detectable in five of six bronchoalveolar lavage fluid samples from patients with adult respiratory distress syndrome at a mean concentration of 465 pg/ml; on the other hand, interleukin-1 beta was not detectable in any of these samples. These results indicate that the relative production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist can be altered depending on the local concentration of both surfactant and plasma.

Biological Products↗
PubMed1995

Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid.

The purpose of this study was to determine whether the formation of docosahexaenoic acid in human cells occurs through a pathway that involves 24-carbon n-3 fatty acid intermediates and retroconversion. Normal human skin fibroblasts synthesized radiolabeled docosahexaenoic acid from [1-(14)C]18:3n-3, [3-(14)C]22:5n-3, [3-(14)C]24:5n-3, and [3-(14)C]24:6n-3. The amount of docosahexaenoate formed was reduced in fibroblasts defective in peroxisomal biogenesis, by 90-100% in Zellweger's syndrome and by 50-75% in infantile Refsum's disease. Fatty acid elongation and desaturation were intact in these mutant cells. No decrease in radiolabeled docosahexaenoic acid production occurred in mutant fibroblasts defective in peroxisomal alpha-oxidation or mitochondrial beta-oxidation, or in normal fibroblasts treated with methyl palmoxirate to inhibit mitochondrial beta-oxidation. Therefore, the retroconversion step in docosahexaenoic acid formation occurs through peroxisomal beta-oxidation in normal human cells. These results demonstrate that the pathway for docosahexaenoic acid synthesis in human cells involves 24-carbon intermediates. The limited ability to synthesize docosahexaenoic acid may underlie some of the pathology that occurs in genetic diseases involving peroxisomal beta-oxidation.

Cells, Cultured↗
PubMed1994

Astrocyte-derived lipoxygenase product evokes endothelium-dependent relaxation of the basilar artery.

The goal of this study was to examine the possible production of vasoactive factors by astrocytes. We consistently observe that rat astroglial cells in suspension produce marked relaxation when added to precontracted rings of intact (but not endothelium-denuded) rabbit basilar artery. The ultimate mediator of this relaxation was endothelium-derived nitric oxide whose synthesis is activated by an as yet unidentified factor(s) produced tonically by astrocytes. The factor is relatively stable, and is not arachidonate, or a product of cyclooxygenase or P450 metabolism. Based upon studies with selective inhibitors, the factor appears to result from 12- or 15-lipoxygenase metabolism, the products of which are known to be vasoactive. In a separate series of experiments, astrocyte-conditioned medium stimulated the production of citrulline from L-arginine by nitric oxide synthase in bovine aortic endothelial cells. The possible significance for central nervous system (CNS) pathophysiology of an astrocyte-derived vasodilator is discussed.

Amino Acid Oxidoreductases↗
PubMed1994

Common structural features of the luxF protein and the subunits of bacterial luciferase: evidence for a (beta alpha)8 fold in luciferase.

The amino acid sequence identity and potential structural similarity between the subunits of bacterial luciferase and the recently determined structure of the luxF molecule are examined. The unique beta/alpha barrel fold found in luxF appears to be conserved in part in the luciferase subunits. From secondary structural predictions of both luciferase subunits, and from structural comparisons between the protein product of the luxF gene, NFP, and glycolate oxidase, we propose that it is feasible for both luciferase subunits to adopt a (beta alpha)8 barrel fold with at least 2 excursions from the (beta alpha)8 topology. Amino acids conserved between NFP and the luciferase subunits cluster together in 3 distinct "pockets" of NFP, which are located at hydrophobic interfaces between the beta-strands and alpha-helices. Several tight turns joining the C-termini of beta-strands and the N-termini of alpha-helices are found as key components of these conserved regions. Helix start and end points are easily demarcated in the luciferase subunit protein sequences; the N-cap residues are the most strongly conserved structural features. A partial model of the luciferase beta subunit from Photobacterium leiognathi has been built based on our crystallographically determined structure of luxF at 1.6 A resolution.

Alcohol Oxidoreductases↗
PubMed1994

IL-1ra suppresses endotoxin-induced IL-1 beta and TNF-alpha release from mononuclear phagocytes.

The proinflammatory effects of lipopolysaccharide (LPS) are modulated in large part through the induction of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) release by mononuclear phagocytes. However, IL-1's target cell effects can be suppressed by IL-1 receptor agonist (IL-1ra). Because mononuclear phagocytes produce and respond to IL-1 via IL-1 receptors, we hypothesized that IL-1ra may also be able to block receptors on IL-1 producer cells and inhibit secondary IL-1-induced IL-1 production. To test this hypothesis, mononuclear cells and alveolar macrophages were stimulated with LPS in the presence of IL-1ra and analyzed for IL-1 beta and TNF-alpha production. For mononuclear cells, IL-1ra inhibited 6-h LPS- and IL-1 alpha-induced IL-1 beta release to 66 +/- 4% (P = 0.001 by paired t test) and 39 +/- 7% (P = 0.0005 by paired t test) of control, respectively. In addition, IL-1ra reduced both LPS- and IL-1 alpha-stimulated IL-1 beta mRNA levels to 78 and 37% of control, respectively. Furthermore, IL-1ra downregulated both LPS and IL-1 alpha-induced TNF-alpha release to 84 +/- 4% (P = 0.012 by paired t test) and 49 +/- 9% (P = 0.001 by paired t test) of control, respectively. Alveolar macrophages demonstrated variable IL-1ra-induced suppression of LPS-stimulated IL-1 beta and TNF-alpha release.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxins↗
PubMed1994

Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and review of the literature.

The clinical, neuroimaging, and neuropathologic features of Schilder's disease in a 17-year-old girl are presented and compared to 11 well-documented cases reported since 1912. The evolution of knowledge about Schilder's disease and the confusion in nomenclature are reviewed. Signs and symptoms in this case and others reported in the literature are nonspecific and may mimic mass lesions. Neuroimaging studies also may mimic brain tumor or abscess; however, the absence of significant edema, the irregular and incomplete ring enhancement, the discrepancy between size of the lesions and the associated mass effect, and the absence of other lesions elsewhere in the brain may help differentiate Schilder's disease from neoplasm, infection, and other demyelinating lesions. Although frozen sections of these lesions are often interpreted as astrocytoma, the inflammatory, primarily histiocytic, nature of Schilder's disease is more easily recognized in paraffin-embedded material. Unique features of this case include multiple unilateral lesions and the cyst-like degeneration present in both lesions. Multiple lesions in Schilder's disease are characteristically bilateral. The examination of aspirated fluid is the first such report in Schilder's disease. The limitation of multiple lesions in our case to one hemisphere calls for reexamination of the restrictive 1985 criteria of Poser for the diagnosis of Schilder's disease.

Adolescent↗
PubMed1994

Educating the family and the patient about nutrition.

Patients and their families deserve sound nutrition advice from primary care practitioners. By using a systematic, community-based approach, the health care provider can integrate nutrition teaching into routine health care. Practitioners should be positive and enthusiastic, should keep nutrition messages simple and food specific, and should recognize that patient lifestyle behaviors will change incrementally and slowly.

Aged↗
PubMed1993

Crystal structure of a flavoprotein related to the subunits of bacterial luciferase.

The molecular structure of the luxF protein from the bioluminescent bacterium Photobacterium leiognathi has been determined by X-ray diffraction techniques and refined to a conventional R-factor of 17.8% at 2.3 A resolution. The 228 amino acid polypeptide exists as a symmetrical homodimer and 33% of the monomer's solvent-accessible surface area is buried upon dimerization. The monomer displays a novel fold that contains a central seven-stranded beta-barrel. The solvent-exposed surface of the monomer is covered by seven alpha-helices, whereas the dimer interface is primarily a flat surface composed of beta-strands. The protein monomer binds two molecules of flavin mononucleotide, each of which has C6 of the flavin isoalloxazine moiety covalently attached to the C3' carbon atom of myristic acid. Both myristyl groups of these adducts are buried within the hydrophobic core of the protein. One of the cofactors contributes to interactions at the dimer interface. The luxF protein displays considerable amino acid sequence homology with both alpha- and beta-subunits of bacterial luciferase, especially the beta-subunit. Conserved amino acid residues shared between luxF and the luciferase subunits cluster predominantly in two distinct regions of the luxF protein molecule. These homologous regions in the luciferase subunits probably share a three-dimensional fold similar to that of the luxF protein.

Amino Acid Sequence↗