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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 541 records · Page 30Linked to original sources
PubMed1985

Attenuation of murine coronavirus infection by ammonium chloride.

Ammonium chloride at a concentration of 20 mM delayed by 4-5 hr the production of virus progeny in mouse L-2 cells infected at high multiplicity with mouse hepatitis virus (MHV). This delay was seen in the production of both intracellular and extracellular virus. However, the final titers were similar to those produced by MHV-infected cells maintained in normal medium. The manifestation of virus-induced cell fusion was similarly found to be delayed, but not otherwise decreased in severity, when ammonium chloride was present in the culture medium. Ammonium chloride caused similar delays in production of virus-specific, positive-sense RNAs and of viral polypeptides. The relative proportions and apparent molecular weights of viral RNAs and polypeptides were similar to those found in MHV-infected cells cultured in normal medium. In vitro translation of endogenously produced viral RNAs in cell extracts, prepared from MHV-infected cells, was not inhibited by ammonium chloride. Thus, ammonium chloride has no specific, inhibitory effect on viral protein synthesis. Ammonium chloride did not reduce the number of virus-infected cells in culture, as monitored by infectious center assay. Analysis of early events in MHV infection showed that ammonium chloride did not affect adsorption or internalization of MHV by L-2 cells. However, the subsequent eclipse phase, as monitored by decline in infectivity of internalized virus inoculum proceeded less efficiently in the presence of ammonium chloride. On the basis of the known inhibitory effects of ammonium chloride on lysosomal/endosomal functions, the results suggest an endosomal mechanism of MHV uncoating. Thus the primary effect of ammonium chloride on MHV infection of L-2 cells is to attenuate virus uncoating, thereby chronologically displacing all subsequent virus-encoded functions.

Ammonium Chloride↗
PubMed1985

Effects of benoxaprofen on the binding to and inactivation of leucoattractants by human polymorphonuclear leucocytes in vitro.

Benoxaprofen was previously found to inhibit the random and leucoattractant-induced migration of human polymorphonuclear leucocytes in vitro by a pro-oxidative mechanism [1]. In this study the effects of benoxaprofen on the binding to PMNL of the synthetic chemotactic tripeptide FMLP, on the oxidative inactivation of this leucoattractant by PMNL and on PMNL chemotaxis, chemokinesis and orientation in an FMLP gradient have been investigated. At concentrations of 10(-5) M (3 micrograms/ml) benoxaprofen inhibited PMNL random and leucoattractant-induced migration and increased PMNL membrane-associated oxidative metabolism and cellular auto-oxidation. These effects of benoxaprofen on PMNL migration and auto-oxidation were prevented by the anti-oxidant cysteine (10(-3) M). Benoxaprofen inhibited both FMLP-induced chemotaxis and chemokinesis but did not affect the binding of radiolabelled FMLP to PMNL or orientation of the cells in a positive gradient of the leucoattractant. Benoxaprofen at concentrations of 5 X 10(-5) M significantly increased the oxidative inactivation of FMLP by PMNL. Inhibition of PMNL migration by benoxaprofen is mediated by the two different pro-oxidative mechanisms, viz. a cell-directed auto-oxidative mechanism and potentiation of the oxidative inactivation of leucoattractants by PMNL.

Chemotaxis, Leukocyte↗
PubMed1985

Extraction of proteins from Saccharomyces cerevisiae ribosomes under nondenaturing conditions.

The differential sensitivity of ribosomal proteins to removal by salts has been studied. Proteins were extracted from the large and small subunits of cytoplasmic ribosomes from Saccharomyces cerevisiae by washing the individual subunits with a series of solutions containing increasing concentrations of NH4Cl (0.74-3.56 M) for a defined time (20 min) at 0 degrees C. The molar ratio of magnesium to ammonium ions of 1:40 was maintained to protect the ribosomal subparticles from complete disassembly. Proteins extracted under each salt condition were analyzed for composition by two-dimensional polyacrylamide gel electrophoresis. The relative quantity of each protein was determined. Most proteins were not removed from the ribosomal particle completely by any one condition, but were preferentially enriched in a single fraction. Whereas most proteins could be solubilized, several proteins remained predominantly or exclusively with the final core particle. The kinetics of protein release from both subunits at a single NH4Cl concentration (0.74 M) were also studied. Release of protein was time dependent, i.e., longer extraction generally removed more of the same proteins. However, prolonged treatment (240 min) of subunits, even at the same salt concentration, resulted in removal of additional species of proteins in varying amounts. Among the ribosomal RNA species, only the 5 S RNA species was released from the ribosomal particles upon treatment.

Ammonium Chloride↗
PubMed1985

The effects of prostaglandin E2 in rapidly growing rats: depressed longitudinal and radial growth and increased metaphyseal hard tissue mass.

The effects of 0, 0.3, 1.0, 3.0, or 6.0 mg of prostaglandin E2 (PGE2)/kg/day administered subcutaneously for 3 weeks to triple fluorochrome-labeled weanling rats are reported. Microradiographs and undecalcified sections of proximal tibiae, tibial shafts, and seventh caudal vertebrae were evaluated by static and dynamic bone histomorphometry techniques. Significant changes were observed only at higher dose levels. Proximal tibial longitudinal growth rates were depressed in doses of 1, 3, or 6 mg PGE2/kg/day. Growth plate thickness and the size of hypertrophic cartilage cells were decreased in animals given 3 and 6 mg of PGE2/kg/day, but the calculated rate of cartilage cell production was unaffected. At doses of 6 mg PGE2/kg/day, periosteal bone apposition rates between Day -1 and Day +19 in both the tibial shafts and caudal vertebral cortices were depressed by less than 25%. Cortical bone mass and endosteal bone apposition rates in the tibial shaft and caudal vertebrae were unaffected. Hard tissue mass in the secondary spongiosa of the proximal tibial metaphysis increased dramatically (28%, 44%, and 60%, respectively) in rats treated with 1, 3, or 6 mg PGE2/kg/day. In addition, the secondary spongiosa contained numerous islands of woven trabecular bone along with an increased number of trabeculae. The study demonstrates that high doses of PGE2 stimulate new woven trabecular bone production and depress longitudinal and radial growth in rapidly growing rats.

1-Carboxyglutamic Acid↗
PubMed1985

Deep inferior epigastric free flap for breast reconstruction after radical mastectomy.

This case illustrates an unusual mastectomy patient in whom the standard alternatives for breast reconstruction were not available. A deep inferior epigastric transverse abdominal free flap was successfully employed. The abundance of tissue provided by this technique enabled reconstruction of a large breast to match the contralateral side.

Abdomen↗
PubMed1985

Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro.

The effects of the antileprosy agents clofazimine and dapsone (1 to 10 micrograms/ml) on the spontaneous and stimulated release of prostaglandin E2 (PG E2) by human polymorphonuclear leukocytes (PMNL) in vitro have been investigated. PMNL were obtained from normal adult volunteers and three patients with leprosy (two borderline lepromatous and one subpolar lepromatous leprosy). The synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) at a concentration of 10(-7) M was used as the stimulant of PG E2 synthesis. None of the test agents at the concentrations used inhibited the binding of radiolabeled FMLP to PMNL. However, dapsone at 5 and 10 micrograms/ml inhibited the spontaneous and FMLP-induced release of PG E2 by PMNL. Clofazimine, on the other hand, significantly increased both the spontaneous and the FMLP-induced synthesis of PG E2 by PMNL. The enhancing effects of clofazimine on FMLP-mediated synthesis of PG E2 were particularly striking and were observed at concentrations of 1 to 10 micrograms of the drug per ml. Measurements of PMNL spontaneous and FMLP-induced synthesis of PG E2 in the presence of both clofazimine and dapsone (5 micrograms/ml) indicated that the two drugs are mutually antagonistic. PMNL from both normal control subjects and patients with leprosy were equally sensitive to these effects of clofazimine and dapsone. The immunostimulatory and immunosuppressive properties of dapsone and clofazimine, respectively, may be related to the opposite effects of these agents on PG E2 synthesis in human leukocytes.

Clofazimine↗
PubMed1985

Comparative evaluation of the enzyme-linked immunosorbent assay in the laboratory diagnosis of brucellosis.

An enzyme-linked immunosorbent assay was adapted to measure total and Brucella abortus-specific immunoglobulin M antibodies. The results were compared with those of conventional serological tests for B. abortus antibody on the sera of a number of normal controls, apparently healthy occupationally exposed workers, and patients with suspected acute brucellosis. Relative to other tests, the B. abortus enzyme-linked immunosorbent assay was found to be both highly sensitive and highly specific. The serological results obtained in occupationally exposed workers indicate a higher "normal range" for this group and therefore a possibility of false-positive results and overdiagnosis. It is therefore important to establish a separate "normal range" for occupationally exposed workers. Investigation of patients with acute brucellosis showed that the enzyme-linked immunosorbent assay for immunoglobulin M was the most sensitive serodiagnostic test and was likely to be of value in the serodiagnosis of acute brucellosis in occupationally exposed workers.

Antibodies, Bacterial↗
PubMed1985

Investigation of the protective effects of the antioxidants ascorbate, cysteine, and dapsone on the phagocyte-mediated oxidative inactivation of human alpha-1-protease inhibitor in vitro.

Oxidants derived from the atmosphere or from activated pulmonary phagocytes mediate functional inactivation of alpha-1-protease inhibitor (alpha-1-PI). Chronic exposure to these oxidants may cause emphysema. In this study we have investigated the effects of the antioxidants ascorbate, cysteine (10(-4) M to 10(-1) M), and dapsone (10(-6) M to 10(-3) M) on the oxidative inactivation of human alpha-1-PI by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. During exposure of alpha-1-PI to stimulated PMNL in the presence of ascorbate and cysteine at concentrations of greater than 10(-4) M and dapsone at greater than 10(-6) M, the elastase inhibitory activity of alpha-1-PI was preserved. However, exposure of the alpha-1-PI to the antioxidants subsequent to PMNL-mediated oxidative inactivation was not associated with reactivation of elastase inhibitory capacity. Ascorbate, cysteine, and dapsone at concentrations that caused 50% protection of alpha-1-PI did not affect degranulation or the binding of radiolabeled leukoattractant to PMNL. It is suggested that the protective effects of the antioxidants are related to their ability to scavenge superoxide and oxidants generated by the PMNL-myeloperoxidase/H2O2/halide system. Because the effects of ascorbate and especially those of dapsone were observed at concentrations of these agents that are attainable in vivo, our results may have clinical significance.

Antioxidants↗
PubMed1984

Mononuclear and polymorphonuclear leucocyte dysfunction in male homosexuals with the acquired immunodeficiency syndrome (AIDS).

In addition to the well-documented abnormalities of cell-mediated immunity we have observed that both polymorphonuclear leucocytes (PMNLs) and mononuclear leucocytes (MNLs) from 3 patients with the acquired immunodeficiency syndrome (AIDS) showed markedly defective migratory responsiveness to leuko-attractants in vitro. Reduced PMNL and MNL chemotaxis is attributable, at least in part, to a serum inhibitor of leucocyte migration, since co-incubation of PMNLs from healthy control subjects with 10% AIDS serum inhibited the migration to leuko-attractants of these cells. This serum-inhibitory effect on leucocyte migration was not due to the presence in AIDS serum of increased levels of prostaglandin E2, cytomegalo-virus or anti-leukocyte antibodies. However, elevated serum immunoglobulin A (IgA) levels were observed in all 3 patients. IgA is a potent inhibitor of PMNL and MNL migration. It is possible that serum inhibitors of leucocyte migration perpetuate the profound immunosuppression characteristic of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Processing of the formyl peptide receptor by HL-60 cells.

Processing of the formyl peptide receptor by differentiated HL-60 cells has been studied using the photoaffinity label N-formyl-Nle-Leu-Phe-Nle-125I-Tyr-Lys-N epsilon-6-(4'-azido-2' -nitrophenylamino)-hexanoate. The receptor on live cells has an apparent molecular weight of 60,000 to 80,000 and possesses one predominant papain cleavage site on the cell exterior yielding a 35,000-Da fragment that contains the binding site. The affinity-labeled receptor was internalized with a t1/2 = 3.2 min at 37 degrees C, a t1/2 = 12 min at 24 degrees C, and was not internalized at 15 degrees C. The internalized receptor was localized in two intracellular compartments with buoyant densities less than that of the plasma membrane. The compartment with the lowest buoyant density was coincident with the Golgi marker galactosyltransferase. Intracellular dissociation of noncovalently bound peptide from the receptor occurred with a t1/2 = 25-28 min. Following a 3-h lag period, internalized affinity-labeled receptor was degraded by a first-order process with a t1/2 = 7 h.

Cell Line↗
PubMed1984

Enhancement of human polymorphonuclear leucocyte motility by erythromycin in vitro and in vivo.

The effects of erythromycin on the migration, phagocytosis and antimicrobial activity of human polymorphonuclear leucocytes (PMNLs) were investigated in vitro. Therapeutic concentrations of erythromycin potentiated PMNL staphylocidal activity without affecting phagocytosis. PMNL random motility and migration to leuco-attractant endotoxin-activated serum (EAS) were significantly enhanced by erythromycin at concentrations of greater than 5 x 10(-5)M (16,5 micrograms/ml). To assess the possible in vivo significance of these findings the same PMNL functions were investigated in healthy adult volunteers before and 90 minutes and 1 week after the ingestion of a single 500 mg tablet of erythromycin stearate. PMNL migration to EAS and antimicrobial activity were significantly increased after ingestion of erythromycin and eventually returned to normal levels. A single intraperitoneal injection of 1,5 mg erythromycin lactobionate significantly increased the mean survival time of mice experimentally infected with Candida albicans. These micro-organisms are resistant to the antimicrobial effects of erythromycin. These findings show that erythromycin possesses nonspecific immunopotentiating properties which may contribute to the antimicrobial activity of this antibiotic.

Adult↗