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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 505 records · Page 28Linked to original sources
PubMed1987

Translational regulation in mouse hepatitis virus infection is not mediated by altered intracellular ion concentrations.

Infection of mouse L-2 fibroblasts with mouse hepatitis virus (MHV) results in strong inhibition of host cell protein synthesis. Since it has been suggested in other virus systems that translational control is modulated by changes in the intracellular ionic environment, we investigated the possible occurrence of similar changes during MHV infection. Membrane permeability to extracellular sodium ions was measured by culturing MHV-infected cells in the presence of 22Na+. Sodium influx into MHV-infected cells rose dramatically from 4 to 6 h post-infection. This influx correlated chronologically with the expression of MHV-mediated cell fusion. Cell fusion was blocked by the addition of a monoclonal antibody against the MHV E2 glycoprotein. This addition also resulted in a reduction in the normal influx of 22Na+, suggesting that E2 expression was responsible, directly or indirectly, for the increased permeability to sodium ions in infected cells. Cultures of MHV-infected cells were labelled with [35S]methionine in the presence of medium supplemented with sodium chloride at final concentrations ranging from 150 mM to 350 mM. Incorporation of radiolabel into proteins decreased with increasing NaCl concentration; however, the ratio of viral to cellular protein synthesis remained relatively constant. Similarly, alteration of intracellular Na+ and K+ levels by treatment of infected cells with ouabain had little effect on the pattern of viral/cellular protein synthesis. Using monoclonal anti-E2 antibody to inhibit Na+ influx, we demonstrated normal inhibition of host cell protein synthesis. We therefore conclude that MHV-induced shut-off of host translation is not mediated by changes in intracellular Na+ concentrations.

Animals↗
PubMed1987

Dithranol mediates pro-oxidative inhibition of polymorphonuclear leukocyte migration and lymphocyte proliferation.

Dithranol (0.01-1 micrograms/ml), but not the auto-oxidized form, caused a dose-related enhancement of the generation of reactive oxidants by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. At the same concentrations dithranol inhibited both PMNL migration to leukoattractants and mitogen-stimulated mononuclear leukocyte (MNL) proliferation. Catalase (50-100 units/ml) protected both PMNL migration and MNL proliferation from dithranol whilst ascorbate and cysteine (1 mM), which maintain dithranol in the biologically active reduced state, potentiated the inhibition. To establish the molecular mechanism of the pro-oxidative activity of dithranol its effects on cytosolic protein kinase C (PKC) activity were investigated. Dithranol caused a dose-related activation of PKC by apparent substitution for 1,2-diolein. These results demonstrate that dithranol, but not its auto-oxidation products, activates PKC which in turn initiates the generation of reactive oxidants by PMNL. Since reactive oxidants are immunosuppressive the therapeutic mechanisms of dithranol may be related to pro-oxidative interactions of this agent with skin phagocytes.

Adult↗
PubMed1987

Pseudocyst of the auricle: compression suture therapy.

Pseudocyst of the auricle is an uncommon, asymptomatic swelling of the ear, resulting from an accumulation of fluid within an unlined intracartilaginous cavity. Numerous therapeutic approaches have been employed in the past with variable success. In this paper we utilized a procedure comprising aspiration of the cystic structure followed by compression with bolstered sutures, with complete resolution of the lesion.

Adult↗
PubMed1987

Prooxidative activities of 10 phenazine derivatives relative to that of clofazimine.

The objective of this study was to investigate the relationship between the antimycobacterial properties of the antileprosy drug clofazimine and its stimulatory effect on the release of reactive oxidants by polymorphonuclear leukocytes by using a variety of phenazine derivatives. The effects of these compounds on myeloperoxidase-mediated iodination, luminol-enhanced chemiluminescence, and the release of superoxide anion by polymorphonuclear leukocytes were investigated. Dissociation of the antimycobacterial and prooxidative effects of clofazimine was possible by manipulation of the chemical group in position 2 of the phenazine molecule. When nitrogen-containing substituents in this position were replaced by oxygen, the mode of the prooxidative action of the compounds was altered.

Clofazimine↗
PubMed1987

An in vivo and in vitro investigation of the phototoxic potential of tenoxicam, a new non-steroidal anti-inflammatory agent.

The phototoxic potential of tenoxicam, a new non-steroidal anti-inflammatory drug (NSAID), was investigated following oral and intradermal administration of the drug. No hypersensitivity responses to ultraviolet radiation (UVR) were observed for either orally or intradermally administered tenoxicam. In a parallel in vitro study, human polymorphonuclear leucocytes (PMNL) and mononuclear leucocytes (MNL) were exposed to UVR in the presence and absence of the NSAIDs tenoxicam, piroxicam and benoxaprofen (10-40 micrograms/ml). The generation of reactive oxidants by control and UVR-treated human PMNL and MNL in the presence and absence of the NSAIDs was measured according to the extent of luminol-enhanced chemiluminescence. Only benoxaprofen activated reactive oxidant generation by PMNL and MNL. The results of these in vitro and in vivo studies show that phototoxicity is unlikely to complicate chemotherapy with tenoxicam.

Administration, Oral↗
PubMed1987

Experience with 8 cases of prenatally diagnosed sacrococcygeal teratomas.

Based on an analysis of eight prenatal diagnoses of sacrococcygeal teratomas and a review of the literature on this condition, sacrococcygeal teratoma can be accurately diagnosed which is related to significant fetal wastage as well as neonatal morbidity and mortality. These tumors are usually benign and the long-term morbidity, but not the overall survival rate, appears to be related to the American Academy of Pediatrics Surgical Section type of tumor. alpha-Fetoprotein can be normal or elevated and acetylcholinesterase in amniotic fluid can be present in spite of the polyhydramnios, but sonography can distinguish these lesions from neural tube defects. Nonimmune hydrops is an ominous sign, particularly in cases detected early in pregnancy. Timing and method of delivery are important considerations for neonatal survival with these lesions. However, normal survival with minimal morbidity is possible even in the largest of sacrococcygeal teratomas.

Cesarean Section↗
PubMed1987

Regulation by the antioxidants ascorbate, cysteine, and dapsone of the increased extracellular and intracellular generation of reactive oxidants by activated phagocytes from cigarette smokers.

The bimodal pattern of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated luminol-enhanced chemiluminescence with distinct early (occurring within 1 min) extracellular and late intracellular oxidative responses was compared in polymorphonuclear leukocytes (PMNL) from asymptomatic cigarette smokers and nonsmoking control subjects. Relative to control PMNL, the PMNL from smokers were hyperreactive to FMLP stimulation with increased generation of both extracellular (p less than 0.025) and intracellular (p less than 0.025) reactive oxidants. Smokers' PMNL also showed increased PMNL-activated superoxide generation and increased apparent receptors for FMLP. The water-soluble antioxidants ascorbate and cysteine (2.5 X 10(-5) M to 2.5 X 10(-4) M) selectively neutralized the extracellular activity of PMNL-derived reactive oxidants. The lipid-soluble antioxidant dapsone (1.25 to 30 micrograms/ml), on the other hand, inhibited both the extracellular and intracellular FMLP-activated chemiluminescence responses in PMNL from smokers and nonsmoking control subjects. Regulation of the increased extracellular and intracellular membrane-associated oxidative responses in PMNL from cigarette smokers is probably an important function of water-soluble and lipid-soluble antioxidants in vivo.

Adult↗
PubMed1986

Biphasic effect of GABAA receptor agonists on prolactin secretion: evidence for two types of GABAA receptor complex on lactotrophes.

The effects of GABA receptor agonists on prolactin secretion in vitro was examined using a rapid superfusion system. GABA and muscimol caused a biphasic effect on prolactin secretion, both components of which were antagonised by bicuculline methiodide, while baclofen had no effect on basal or stimulated secretion, demonstrating the GABAA receptor specificity of both components. Homocarnosine caused only inhibition of secretion, and a range of partly rigid GABA analogues were relatively poor at causing stimulation of secretion. Both effects of muscimol were antagonised by low-chloride medium and the anion channel blocker DIDS, but strychnine and picrotoxinin were both potent and selective antagonists of the stimulatory effect. These results demonstrate a novel biphasic effect of GABAA agonists or prolactin secretion, the two components of which appear to be independent and mediated by different types or states of GABAA receptor/chloride channel complex.

Animals↗
PubMed1986

Partial reassembly of yeast 60 S ribosomal subunits in vitro following controlled dissociation under nondenaturing conditions.

Previously it has been shown that 12 of the yeast ribosomal proteins were extractable from 60 S subunits under a specific nondenaturing condition [J. C. Lee, R. Anderson, Y. C. Yeh, and P. Horowitz (1985) Arch. Biochem. Biophys. 237, 292-299]. In the present paper, we showed that these proteins could be reassembled with the corresponding protein-deficient core particles to form biologically active ribosomal subunits. Effects of time, temperature, and varying concentrations of monovalent cations, divalent cations, cores, and ribosomal proteins on reconstitution were examined. Reconstitution was determined by binding of radiolabeled proteins to the nonradiolabeled cores as well as activity for polypeptide synthesis in a cell-free protein-synthesizing system. The optimal conditions for reconstitution were established. Whereas the core particles were about 10-20% as active as native 60 S subunits in an in vitro yeast cell-free protein-synthesizing system, the reconstituted particles were 80% as active. The activity of the reconstituted particles was proportional to the amount of extracted proteins added to the reconstitution mixture. About 55 +/- 7% of the core particles recombined with the extracted proteins to form reconstituted particles. These reconstituted particles cosedimented with native 60 S subunits in glycerol gradients and contained all of the 12 extractable proteins.

Ammonium Chloride↗
PubMed1986

Long term model for evaluation of myocardial metabolic recovery following global ischemia.

Myocardial ATP levels remain depressed following significant periods of ischemia (Isc) despite reperfusion (Rpf). Neither the rate of in vivo ATP return following global Isc nor the factors which influence recovery have been defined. In order to determine the time course to complete the return of ATP levels and evaluate methods of enhancing recovery of ATP levels, we have devised a chronic canine model of global Isc. In this model serial ventricular biopsies can be taken in the awake animal over several days without reoperation which allows an investigation of the recovery of the myocardium following a uniform global insult to be performed. Recovery of ATP levels has been shown to depend, at least in part, on the availability of precursors and the activity of the ATP regenerating enzymes. Because complete recovery of ATP levels takes days, short term (hours) models have limitations. Previous attempts at enhancing ATP recovery following Isc have been only partially successful because either the degree of depression was not great or the period of observation was short, resulting in incomplete return. To identify the best precursor choice, we previously measured the activity of the AMP regenerating enzymes, adenosine kinase (AdK) (adenosine----AMP) and adenine phosphoribosyl transferase (APRT) (adenine----AMP). Because APRT activity was 20 fold higher than AdK with similar Km values for substrates, it appeared that adenine (A) is preferred to adenosine for AMP regeneration in the dog's myocardium. The formation of 5-phosphoribosyl 1-pyrophosphate (PRPP) may also be rate limiting and, therefore, the effect of ribose (R) on ATP recovery was also evaluated. Recovery of ATP levels was assessed in three groups: (1) normal saline (NS), (2) A (20 mM) in normal saline (A/NS) or (3) A with R (80 mM) in normal saline (A/R) were infused (1.0 ml/min) into the right atrium of dogs for 48 hours following Isc. In all groups, ATP levels fell to between 46-60% of pre-Isc levels during Isc. In the NS dogs, ATP levels continued to fall slightly to 46% pre-Isc levels during the first four hours of Rpf after Isc. By 24 hours no appreciable recovery had occurred and the measured ATP was only 51% of the pre-Isc value. Even by seven days, ATP had not returned fully, and by extrapolation, complete recovery required 9.9 +/- 1.4 days. Treated dogs showed, however, that ATP recovery could be significantly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗
PubMed1986

Fatty acid distribution in the phospholipids of Francisella tularensis.

Francisella tularensis, LVS (live vaccine strain) grown in a chemically defined medium was found to have a lipid content of 21% by dry weight. The two major phospholipids were identified as phosphatidylethanolamine (PE; 76%) and phosphatidylglycerol (PG; 24%) by thin layer chromatographic analysis, staining characteristics and quantitative chemical analyses of fatty acid, phosphate and glycerol constituents. PE contained a high proportion of 24:0 fatty acid, with lesser amounts of 24:1, 22:0 and 10:0. The major fatty acids of PG were 18:1 and 22:0. Hydroxy fatty acids, which are prominent components of F. tularensis, were conspicuously lacking in these phospholipids; it is therefore concluded that hydroxy fatty acids are constituents of other structures of the organism.

Bacterial Vaccines↗
PubMed1986

Clofazimine-mediated stimulation of prostaglandin synthesis and free radical production as novel mechanisms of drug-induced immunosuppression.

The effects of clofazamine (3-(p-chloroanilino)-10-(p-chlorophenyl)-2, 10-dihydro-2-(isopropylimino)-phenazine) at concentrations of 0.625-20 micrograms/ml on the mitogen-induced transformation, luminol-enhanced chemiluminescence, arachidonic acid metabolism and sulphydryl content of human mononuclear leucocytes (MNL) were investigated in vitro. The drug at all concentrations tested decreased MNL sulphydryl content and inhibited mitogen-induced transformation. Clofazimine increased the spontaneous luminol-enhanced chemiluminescence and activated the arachidonic acid cascade in MNL. The anti-oxidants ascorbic acid and cysteine and the prostaglandin (PG) synthesis inhibitor indomethacin were used individually and in combination to identify the primary mediators of the anti-proliferative effects of clofazimine on MNL. Combinations of an anti-oxidant with a PG synthesis inhibitor completely protected MNL from clofazimine mediated inhibition of mitogen-induced transformation. These results show that the anti-proliferative activity of clofazimine is related to both the pro-oxidative and PG synthesis enhancing effects of the drug on MNL.

Clofazimine↗
PubMed1986

Clofazimine-mediated regulation of human polymorphonuclear leukocyte migration by pro-oxidative inactivation of both leukoattractants and cellular migratory responsiveness.

The effects of clofazimine (0.15-20 micrograms/ml) on the spontaneous and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-stimulated migration, membrane-associated oxidative metabolism, degranulation and production of prostaglandin (PG) E2 by human polymorphonuclear in vitro have been investigated. Clofazimine at concentrations of 0.3 microgram/ml and greater significantly increased both the spontaneous and FMLP-stimulated chemiluminescence (CL), hexose monophosphate shunt (HMS) activity, myeloperoxidase-mediated protein iodination, auto-iodination, degranulation and PGE2 production by PMNL. At the same concentrations clofazimine inhibited both random and leukoattractant-induced migration of PMNL. Inhibition of PMNL migration by clofazimine was due to both a cell-directed auto-oxidative mechanism and by functional inactivation of FMLP. Clofazimine mediated inhibition of PMNL migration was prevented by the anti-oxidants cysteine and dapsone but not by the potent inhibitors of PG synthetase indomethacin and piroxicam. Anti-oxidants also protected FMLP from functional inactivation by clofazimine-exposed PMNL. Clofazimine increased both the spontaneous and FMLP-stimulated production of PGE2 by PMNL from four children with chronic granulomatous disease (CGD). Clofazimine is not an oxidising agent nor did it stimulate membrane-associated oxidative metabolism in CGD or NaF-pulsed normal PMNL. These data show that clofazimine-mediated inhibition of PMNL migration is dependent on intact cellular membrane-associated oxidative metabolism. Clofazimine is therefore a pro-oxidative anti-inflammatory agent.

Adult↗
PubMed1986

Anatomic correction of double-outlet right ventricle with subpulmonary ventricular septal defect (the "Taussig-Bing" anomaly).

Seven patients with double-outlet right ventricle and subpulmonary ventricular septal defect (the Taussig-Bing anomaly) underwent anatomical repair at the arterial level with transfer of the coronary arteries. At the time of operation, patient ages ranged from 6 weeks to 33 months (mean 14.1 months) and weight ranged from 3.7 to 11.5 kg (mean 7.0 kg). Four patients had prior pulmonary artery banding: Two of these four also had coarctation repairs, and one had a Blalock-Hanlon septectomy. Three different patterns of coronary artery distribution were encountered. Five patients had side-to-side great arteries, and two had more or less anteroposterior great arterial relationships. There was one operative death (14.3%: 70% confidence limits 1.9 - 40.7%) resulting from muscular subvalvular right ventricular outflow tract obstruction (RVOTO). There have been no late deaths in the six survivors followed 6 to 31 months postoperatively (mean 14.8 months). One patient required closure of a residual ventricular septal defect (VSD) and infundibular resection for RVOTO 4 months postoperatively. All other survivors are functionally NYHA Class I. Five of the six survivors have undergone postoperative catheterization (mean interval 5.8 months). There was no aortic insufficiency and good ventricular function in all patients. In addition to the patient with the residual VSD, two other asymptomatic patients had mild or moderate RVOTO. Compared with alternative surgical procedures for this anomaly, anatomic correction has the advantages of acceptable operative mortality, use of the left ventricle as the systemic ventricle, no need for extracardiac conduits, and applicability to patients with all variations of coronary artery and great artery anatomy.

Child, Preschool↗