Search PubMed⌕ Search

Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 343 records · Page 19Linked to original sources
PubMed1993

Membrane and phospholipid binding by murine coronaviral nucleocapsid N protein.

Evidence is presented which indicates that membrane binding of the murine coronavirus, mouse hepatitis virus (MHV) nucleocapsid (N) protein is mediated by certain lipids. Binding of N protein to membranes of mouse fibroblast L-2 cells is very specific and occurs under conditions in which no other viral or cellular proteins show detectable binding. Binding occurs with both free and nucleocapsid-associated N protein, arguing for membrane-binding sites on the N protein itself, rather than on RNA. Binding of N protein also occurs to membranes in the absence of MHV matrix (M) protein which is known to interact with the N protein. Both non-viral, single-stranded RNA and DNA inhibit membranes. Of various phospholipids tested, cardiolipin was the most effective in inhibiting membrane binding. The N protein was also shown to bind directly to phospholipid liposomes containing cardiolipin as well as to liposomes containing total lipids extracted from mouse L-2 cells. Because of certain structural similarities between phospholipids and nucleic acids, we speculate that membrane lipid association of the N protein may compete for RNA binding sites on the N protein. Such a mechanism may be important for processes such as nucleocapsid uncoating and nucleocapsid assembly. Most interestingly the properties of phospholipid and nucleic acid binding are markedly similar to those recently described for the bacterial DNA-binding proteins DnaA and recA.

Animals↗
PubMed1993

Involvement of lipids in membrane binding of mouse hepatitis virus nucleocapsid protein.

Evidence is presented which indicates that membrane binding of the MHV nucleocapsid (N) protein is influenced by membrane lipid composition. Binding of N protein to membranes of mouse fibroblast L-2 cells is very specific and occurs under conditions in which no other viral or cellular proteins show detectable binding. Binding occurs rapidly and does not require the presence of divalent cations such as Ca++ or Mg++. Purified phospholipid liposomes compete against N protein binding to membranes. Phospholipids consisting of cardiolipin are the most effective in inhibiting membrane binding. Because of certain structural similarities between phospholipids and nucleic acids, we speculate that membrane lipid association of the N protein may compete for RNA binding sites on the N protein. Such a mechanism may be important for processes such as nucleocapsid uncoating and nucleocapsid assembly.

Animals↗
PubMed1993

Diffuse Lewy body disease with immediate post-partum onset.

A previously healthy 27 years-old woman developed psychotic depression and parkinsonism shortly after delivery of her first child. Her neuropsychiatric symptoms progressed to dementia and she died 5 years after onset. Diffuse Lewy body disease was found at autopsy. This case is unusual because of the early age of onset and the abrupt development of symptoms following pregnancy.

Adult↗
PubMed1993

Psychometric considerations in evaluating health-related quality of life measures.

How does one determine if a measure of health-related quality of life (HRQL) is adequate for clinical trials? Psychometric methods are frequently used to answer this question. What is psychometrics all about? In this paper we address these questions, discussing common psychometric evaluation procedures applied to HRQL measures. Specifically, we discuss issues regarding the evaluation of reliability and validity (including responsiveness).

Cross-Cultural Comparison↗
PubMed1993

Developing and evaluating cross-cultural instruments from minimum requirements to optimal models.

In the age of increased international collaboration in medical research, the necessity of having at hand cross-culturally applicable instruments for the assessment of health-related quality of life (HRQL) in clinical trials has been voiced. Several important theoretical bases leading to cultural bias in HRQL measurement include differences in definitions of HRQL across national and cultural contexts, levels of observation relied upon to indicate HRQL states, and the significance or weight placed upon the various HRQL states or dimensions measured. Despite a growing literature on the development and evaluation of existing HRQL measures in other cultures, comprehensive sets of procedures or requirements for the international part of development and evaluation are lacking. This paper reviews major approaches to developing international HRQL measures, and discusses various methods and criteria that have been recommended for evaluating measurement equivalence in comparisons of research across national and cultural contexts. A summary of recent trends and advances in international HRQL assessment is presented.

Bias↗
PubMed1993

Vitamin E protects mononuclear leucocyte DNA against damage mediated by phagocyte-derived oxidants.

The protective effects of physiological concentrations (3-12.5 micrograms/ml) of vitamin E (VE, dl-alpha-tocopherol) on the formation of DNA single-strand breaks in mononuclear leukocytes (MNL) in close proximity to activated phagocytes have been investigated in vitro. Human neutrophils, activated by phorbol myristate acetate (PMA), induced DNA-strand breaks in neighbouring lymphocytes. Vitamin E caused dose-related protection of MNL DNA against phagocyte-mediated oxidative damage. This apparently novel protective activity of vitamin E is due primarily to the inhibitory effects of this agent on the generation of reactive oxidants by activated neutrophils and is apparently unrelated to the classical oxidant-scavenging properties of VE.

Adult↗
PubMed1993

Effects of clofazimine analogues and tumor necrosis factor-alpha individually and in combination on human polymorphonuclear leukocyte functions in vitro.

In the present study the individual and interactive effects of clofazimine, or three analogues of this agent (selected on the basis of similar or superior pro-oxidative properties: B669, B746 and B4021) and human recombinant TNF-alpha on the generation of antimicrobial oxidants by human polymorphonuclear leukocytes (PMNL), as well as release of granule enzymes from these cells, were investigated in vitro. All four riminophenazines at the concentrations tested (0.5 and 1.0 micrograms/ml) significantly increased myeloperoxidase (MPO)-mediated iodination, superoxide (0(2).-) generation, oxygen (0(2)) consumption and chemiluminescence (CL), as well as the release of both primary and secondary granule contents (measured as the release of MPO, lysozyme and vitamin B12-binding protein) by stimulated PMNL. Similar, but less impressive effects were observed with TNF-alpha (0.4-50.0 ng/ml). When PMNL were preincubated with both TNF-alpha and clofazimine or its analogues, the observed stimulation of cellular oxidative metabolism and granule enzyme release was at least additive in many assays. These data demonstrate that the spectrum of effects of clofazimine and its analogues on PMNL closely resemble those of TNF-alpha. Furthermore, TNF-alpha potentiates the pro-oxidative effects of clofazimine and its analogues on PMNL. Among the riminophenazines tested, clofazimine and B669 appear to be the most potent pro-oxidative agents for PMNL.

Adult↗
PubMed1993

Functional and urodynamic characteristics of an ileal neobladder.

We examined the urodynamic characteristics and symptoms of 28 patients who had undergone the Stanford pouch bladder substitution following cystoprostatectomy. Urodynamics were obtained a mean of 18 months (range 6 to 43) after construction of the neobladder. Mean cystometric capacity was 699 cc (range 366 to 1,370). All patients voided by the Valsalva maneuver and achieved good peak flow rates (mean 19 cc per second). Of the patients 23 emptied to near completion with a mean post-void residual of 34 cc, while 5 had post-void residuals of greater than 150 cc (mean 630 cc). The neobladders demonstrated good compliance for the storage of urine, with a mean basal pressure of less than 15 cm. water at volumes of less than 500 cc at which most bladders function, and of 22.4 cm. water (range 1 to 72) at 100% capacity. Phasic neobladder contractions were present during filling cystometrography. While the number increased at higher neobladder volumes, the mean length and mean pressure did not. The mean pressure of contractions was less than 40 cm. water at lower and higher volumes. Daytime continence was attained in 26 of 28 patients (93%), while 17 (61%) attained nighttime continence. Of these 17 patients 14 (82%) had to void at least once at night to stay dry. Daytime incontinent patients had decreased neobladder compliance at high volumes compared to daytime continent patients (p < 0.05) but there was no difference in the maximal urethral closure pressure or the pressure of phasic contractions between these 2 groups. No difference was found in any urodynamic parameter between nighttime continent and incontinent patients. Patients with poor emptying ability (defined as a post-void residual of more than 150 cc) had increased neobladder compliance relative to patients with good emptying ability, as well as a statistically significant increased capacity (1,067 cc versus 623 cc). There was no difference in any important urodynamic parameter between patients who had and had not received postoperative chemotherapy. We conclude that a neobladder constructed from detubularized ileum achieves adequate capacity at low pressures with a satisfactory continence rate. Most patients empty the bladder to completion by Valsalva's maneuver. Low compliance at high volumes appears to be a factor in daytime incontinence.

Adult↗
PubMed1993

In vivo parthenogenetic activation of ovulated oocytes in a marsupial, Sminthopsis crassicaudata.

The occurrence of in vivo parthenogenesis is documented for laboratory-bred individuals of the Australian dasyurid marsupial, Sminthopsis crassicaudata. About 30% of females that had been isolated from males for a greater period of time than the length of pregnancy were found, on dissection of their uteri, to have embryos present. The embryos were surrounded by a mucoid coat and shell membrane and at least the first two cleavage divisions occurred normally. After this time, however, unequal cleavage divisions appeared to result. The parthenogenesis that takes place may be initiated as a result of activation of ageing ovulated oocytes. Its frequent occurrence may prove useful in a study of maternal and paternal contributions to early embryonic development in the species.

Animals↗
PubMed1993

Suppression of non-esterified fatty acids and triacylglycerol in experimental animals by the adenosine analogue GR79236.

1. This is the first description of the metabolic activity of a novel adenosine A1-receptor agonist, GR79236. GR79236 inhibited catecholamine-induced lipolysis in human, rat and dog isolated adipocytes. 2. Oral administration of GR79236 (0.1-10 mg/kg) to fed rats induced minimal changes in the plasma concentration of non-esterified fatty acids and in the blood concentrations of glucose and lactate. 3. Intravenous infusion of GR79236 to fasted pithed rats, or oral administration of GR79236 to fasted conscious rats and dogs, produced time- and dose-dependent decreases in the plasma non-esterified fatty acid concentration. In the fasted rats, doses of GR79236 that lowered plasma levels of non-esterified fatty acids also produced hypotriglyceridaemia and anti-ketotic effects. 4. Only in the pithed rats were acute effects on the plasma glucose and lactate concentrations observed. Hypoglycaemia and hyperlactataemia occurred over the dose range studied (1 x 10(-11)-1 x 10(-8) mol min-1 kg-1). 5. This profile of activity suggests that compounds such as GR79236 might be agents which can be used to define the role of excessive lipolysis in experimental (and human) pathophysiology.

Adenosine↗
PubMed1993

An in vitro comparison of the effects of the prooxidative riminophenazines clofazimine and B669 on neutrophil phospholipase A2 activity and superoxide generation.

The effects of the antimycobacterial agent clofazimine and its experimental analogue B669 on the phospholipase A2 activity of and superoxide generation by human blood neutrophils were investigated in vitro. Coincubation of neutrophils with clofazimine or B669 (1-10 micrograms/mL) was accompanied by a dose-related increase in the release of both [3H]lysophosphatidylcholine (LPC) and [3H]arachidonate (AA). Both agents (1 microgram/mL) also increased the production of superoxide by resting and FMLP-stimulated neutrophils. Addition of reagent AA and especially LPC to neutrophils mimicked the effects of the riminophenazines, while alpha-tocopherol, a lysophospholipid complex-forming agent, neutralized the prooxidative interactions of clofazimine and B669 with these cells. These observations demonstrate that LPC, and to a lesser extent AA, generated during exposure of human neutrophils to clofazimine or B669 are the primary mediators of the prooxidative interactions of these riminophenazines with phagocytes.

Adult↗
PubMed1993

Antigen processing: where tumor-specific T-cell responses begin.

It is well established that tumor-specific CD8+ T cells have the capacity to prevent and cure malignancies in animals under experimental conditions. This has raised expectations that it will prove possible to achieve similar successes with human cancers. CD8+ T cells recognize peptides of 8-10 residues derived from cytosolic proteins that are bound to the class I molecules of the major histocompatibility complex. To most effectively manipulate the T-cell response to tumor cells, it is essential to understand the means by which the peptide-class I complex is created in cells. An overview of this process is provided with an emphasis toward the recent findings made by our laboratory.

Animals↗
PubMed1993

Activation of neutrophil membrane-associated oxidative metabolism by ultraviolet radiation.

Exposure of human neutrophils to ultraviolet radiation (UVR) in vitro was accompanied by activation of superoxide generation and preferential release of secondary granules. These pro-oxidative interactions of UVR with neutrophils were dependent on intact cellular membrane-associated oxidative metabolism and were mediated almost exclusively by the UVB component of UVR. Irradiation of neutrophils was also associated with release of arachidonic acid from membrane phospholipids, implicating involvement of phospholipase A2 (PLA2) in the pro-oxidative activity of UVR. The pro-oxidative interactions of UVR with neutrophils were mimicked by coincubation of the cells with reagent arachidonate or lysophosphatidylcholine (LPC), whereas the PLA2 inhibitor 4-p-bromophenacyl bromide, as well as the LPC- and arachidonate complex-forming agent alpha-tocopherol, inhibited these pro-oxidative interactions of UVR with phagocytes. Because phagocyte-derived reactive oxidants are cytotoxic, immunosuppressive, and carcinogenic, these agents are potential mediators of UVR-mediated tissue damage and tumorigenesis.

Arachidonic Acid↗
PubMed1993

Identification of an immunodominant linear neutralization domain on the S2 portion of the murine coronavirus spike glycoprotein and evidence that it forms part of complex tridimensional structure.

Numerous studies have demonstrated that the spike glycoprotein of coronaviruses bears major determinants of pathogenesis. To elucidate the antigenic structure of the protein, a panel of monoclonal antibodies was studied by competitive ELISA, and their reactivities were assayed against fragments of the murine coronavirus murine hepatitis virus strain A59 S gene expressed in prokaryotic vectors. An immunodominant linear domain was localized within the predicted stalk, S2, of the peplomer. It is recognized by several neutralizing antibodies. Other domains were also identified near the proteolytic cleavage site, in the predicted globular head, S1, and in another part of the stalk. Furthermore, competition results suggest that the immunodominant functional domain forms part of a complex three-dimensional structure. Surprisingly, some antibodies which have no antiviral biological activities were shown to bind the immunodominant neutralization domain.

Amino Acid Sequence↗
PubMed1993

Performance characteristics and interanalyzer variability of PO2 measurements using tonometered human blood.

We performed a side-by-side comparison of the ability of four blood gas analyzers (IL-1312, Corning-178, AVL-995, and ABL-330) to measure PO2 across a wide range under controlled laboratory conditions. Samples of fresh whole human blood, tonometered with analytic quality gas, were prepared with partial pressures of oxygen from 0 to 283 mm Hg. Fifteen determinations were made at 16 levels of tonometric PO2 (tPO2) on each of the four blood gas analyzers. The bias, precision, and root mean squared error (RMSE) of the PO2 measurement relative to tPO2 were determined for each analyzer at each tPO2 level. Mean bias and precision across the range tested were 2.78 +/- 1.29 mm Hg (IL), -0.35 +/- 1.91 (Corning), 2.14 +/- 1.43 (AVL), and 3.00 +/- 1.47 (ABL). RMSE was 3.28, 2.61, 3.57, and 2.41 for IL, AVL, ABL, and Corning, respectively. Percent RMSE (RMSE/tPO2 x 100%), ranged from 0.9% (AVL at 75 mm Hg PO2 and IL at 283 mm Hg tPO2) to 9.1% (IL at 29 mm Hg tPO2). Three analyzers (AVL, ABL, and Corning) showed a statistically significant (p < 0.0001) correlation between RMSE and tPO2, and no correlation between percent RMSE and tPO2. This demonstrates that, for these instruments, accuracy is a function of the magnitude of the tPO2 value. IL did not show a significant correlation between RMSE and tPO2 but did demonstrate a significant negative correlation (r = -0.78, p > 0.001) between percent RMSE and tPO2, indicating that, for this analyzer, accuracy is not a function of tPO2. The differences in PO2 measurements between pairs of analyzers were also examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗