Search PubMed⌕ Search

Biomedical subjects

E G Moore

Publications and source records attributed to E G Moore.

At least 19 recordsLinked to original sources
PubMed2001

Photoinduced electron transfer and electronic energy transfer in naphthyl-appended cyclams.

A series of novel macrocyclic tetraaza ligands that incorporate a naphthalene moiety as a photoactive chromophore have been prepared and structurally characterized as their Cu(II) complexes. Variable-temperature photophysical studies have concluded that the luminescence quenching evident in the Cu(II) complexes is due to intramolecular electronic energy transfer (EET). In their free-base forms, these ligands undergo reductive luminescence quenching via photoinduced electron transfer (PET) reactions, with proximate amine lone pairs acting as electron donors. Consequently, the emission behavior can be modulated by variations in pH and/or the presence of other Lewis acids such as Zn(II).

Journal Article↗
PubMed2000

Abnormalities of flavin monooxygenase as an etiology for sideroblastic anemia.

We postulated that a deficiency of flavin monooxygenase (FMO)-a ferrireductase component of cells-could produce sideroblastic anemia. FMO is an intracellular ferrireductase which may be responsible for the obligatory reduction of ferric to ferrous iron so that reduced iron can be incorporated into heme by ferrochelatase. Abnormalities of this mechanism could result in accumulation of excess ferric iron in mitochondria of erythroid cells to produce ringed sideroblasts and impair hemoglobin synthesis. To investigate this hypothesis we obtained blood from patients with sideroblastic anemia and normal subjects. Extracts of peripheral blood lymphocytes were used to measure ferrireduction by utilization of NADPH. Lymphoid precursors are reported to accumulate iron in mitochondria similarly to erythroid precursors. Utilization of lymphoid precursors avoided the need for bone marrow aspirations. We studied three patients with sideroblastic anemia. One patient and his asymptomatic daughter had a significant decrease in ferrireductase activity. They also had markedly diminished concentrations of FMO in lymphocyte protein extracts on Western blots. This was accompanied by increased concentration of mobilferrin in the extracts. These results suggest that abnormalities of FMO and mobilferrin may cause sideroblastic anemia and erythropoietic hemochromatosis in some patients.

Aged↗
PubMed2000

African-American fathers: perceptions of two generations.

The purpose of this study was to determine how African-American fathers of 10-14-years-olds viewed their assets and limitations as parents, and to find out how children from this age group saw the parent performance of their fathers. The Parent Success Indicator was administered to 102 fathers and to 104 adolescents. Significant differences were found between generations on five of six subscales. The independent variables entering the greatest effect on how both generations perceived parental success were amount of time father and child spent together, having an adult at home when a child returns from school, and gender of child.

Adolescent↗
PubMed2000

Separate pathways for cellular uptake of ferric and ferrous iron.

Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron. We postulate that ferric iron was transported into cells via beta(3)-integrin and mobilferrin (IMP), whereas ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp-2). These conclusions were documented by competitive inhibition studies, utilization of a beta(3)-integrin antibody that blocked uptake of ferric but not ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue culture cells that showed enhanced uptake of ferrous iron and manganese but neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing decreased iron and manganese but not zinc or copper, and data showing that the addition of reducing agents to tissue culture media altered iron binding to proteins of the IMP and DMT-1 pathways. Although these experiments show ferric and ferrous iron can enter cells via different pathways, they do not indicate which pathway is dominant in humans.

Amino Acid Substitution↗
PubMed1999

UV resonance Raman spectra reveal a structural basis for diminished proton and CO2 binding to alpha,alpha-cross-linked hemoglobin.

UV resonance Raman difference spectra between ligated and deoxyhemoglobin contain tryptophan and tyrosine signals which arise from quaternary H-bonds in the T state, which are broken in the R state. These H-bonds are unaffected by bis(3,5-dibromosalicyl) fumarate cross-linking at the Lys alpha 99 residues, which prevents dissociation of Hb tetramers to dimers. However, when the pH is lowered from 9.0, or when NaCl is added, intensity is diminished for the tyrosine Y8 and tryptophan W3 bands of cross-linked deoxyHb, but not of native deoxyHb. This effect is attributed to weakening of tertiary H-bonds involving Tyr alpha 140 and Trp alpha 14, when the T state salt bridge between Val alpha 1 and Arg alpha 141 is formed via protonation of the terminal amino group and anion binding. The Tyr alpha 140-Val alpha 93 H-bond connects the Arg alpha 141-bearing H helix with the Lys alpha 99-bearing G helix. Weakening of the H-bond reflects a tension between the fumarate linker and the salt-bridge. This tension inhibits protonation of the Val alpha 1 amino terminus, thus accounting for the diminution of both proton [Bohr effect] and CO2 binding in the T state as a result of cross-linking.

Anions↗
PubMed1999

Peer and self-evaluation of teamwork skills.

The increasing reliance of corporations on teamwork and peer evaluation of job performance requires the acquisition of these skills in high school. An approach called the Peer and Self-Evaluation System (PSES) informs teachers about group interaction from the student view. This strategy enables students to identify and record teamwork skills demonstrated by peers and themselves in co-operative activities. Based upon these observations, which are kept anonymous, students get confidential feedback about personal strengths and limitations. Field testing of the system with 300 high school students and their teachers confirmed its worth. Moreover, the findings showed that girls were identified by the boys and by themselves as having greater co-operative teamwork skills. The PSES method of evaluating group work can be used in most subject matter areas, results are appropriate for student and teacher portfolios, and outcomes can guide the united effort of parents and teachers

Adolescent↗
PubMed1999

Iron absorption and transport.

Iron is vital for living organisms because it is essential for multiple metabolic processes to include oxygen transport, DNA synthesis, and electron transport. However, iron must be bound to proteins to prevent tissue damage from free radical formation. Thus, its concentrations in body organs must be regulated carefully. Intestinal absorption is the primary mechanism regulating iron concentrations in the body. Three pathways for intestinal iron uptake have been proposed and reported. These are the mobilferrin-integrin pathway, the divalent cation transporter 1 (DCT-1) [or natural resistance-associated macrophage protein (Nramp2)] pathway, and a separate pathway for uptake of heme by absorptive cells. Each of these pathways are incompletely described. However, studies with blocking antibodies, observations in rodents with disorders of iron metabolism, and studies in tissue culture cells suggest that the DCT-1 pathway is dominant in embryonic cells and is involved with cellular uptake of ferrous iron, whereas the mobilferrin-integrin pathway facilitates absorption of dietary inorganic ferric iron. Thus, there are separate pathways for cellular uptake of ferric and ferrous inorganic iron. Body iron can enter intestinal cells from plasma via basolateral membranes containing the classical transferrin receptor pathway with a high affinity for holotransferrin. This keeps the absorptive cell informed of the state of iron repletion of the host. Intestinal mucosal cell iron seems to exit the cell via a distinct apotransferrin receptor and a newly described protein named hephaestin. Unlike the absorptive surface of intestinal cells, most other cells possess transferrin receptors on their surfaces and the vast majority of iron entering these cells is transferrin associated. There seem to be 2 distinct pathways by which transferrin iron enters nonintestinal cells. In the classical clathrin-coated pitendosome pathway, iron accompanies transferrin into the cell to enter a vesicle, which releases the iron to the cytosol with acidification (high affinity, low capacity). Under physiological conditions, a second transferrin associated pathway (low affinity, high capacity) exists which has been named the transferrin receptor independent pathway (TRIP). How the TRIP delivers iron to cells is incompletely described. In addition, tissue culture studies show that nonintestinal cells can accept iron from soluble iron salts. This occurs via the mobilferrin-integrin and probably the DCT-1 pathways. Cellular uptake of iron from iron salts probably occurs in iron overloading disorders and may be responsible for free radical damage when the iron binding capacity of plasma is exceeded. Radioiron entering the cell via the heme and transferrin associated pathways can be found in isolates of mobilferrin/paraferritin and hemoglobin. This interaction probably occurs to permit NADPH dependent ferrireduction so iron can be used for synthesis of heme proteins. Production of heme from iron delivered via these routes indicates functional specificity for the pathways.

Animals↗
PubMed1998

Absence of immunogenicity of diaspirin cross-linked hemoglobin in humans.

Diaspirin cross-linked hemoglobin (DCLHb) is an intramolecularly cross-linked hemoglobin-based oxygen carrier being developed as a therapy for acute blood loss. We report here the absence of immunogenicity of DCLHb in patients enrolled in phase II and III clinical trials of DCLHb. Two very sensitive immunoassays, an enzyme-linked immunosorbent assay (ELISA) and a Western blot assay, were developed and validated for this assessment. The DCLHb-antibodies used in these assays were raised in monkeys, had similar affinities for DCLHb and native human hemoglobin (SFHb), and showed cross-reactivity for subunits of DCLHb and SFHb on the Western blot, suggesting that these antibodies were elicited as a xenogenic response to the protein. In the ELISA, the optical density of a patient sample exposed to DCLHb-coated wells was compared with that of the patient sample exposed to carbonate buffer-coated wells; an optical density ratio of 1.4 was established for discriminating between a positive (reactive) or negative DCLHb antibody response. To date, all of the more than 300 patient specimens (preinfusion and postinfusion) from clinical trials have exhibited a ratio of less than 1.4, confirming the lack of preexisting antibodies to DCLHb and clearly showing the absence of DCLHb antibodies after exposure to this new biologic entity. There has been no requirement for use of the confirmatory Western blot assay. Taken together, the results from this study indicate DCLHb is not immunogenic in humans at doses evaluated clinically.

Animals↗
PubMed1998

Iron absorption and cellular transport: the mobilferrin/paraferritin paradigm.

Dietary inorganic iron is mostly ferric iron. This is solubilized at the acid pH level of the stomach where it chelates mucins and certain dietary constituents to keep them soluble and available for absorption in the more alkaline duodenum. Mucosal uptake of iron is facilitated by a beta 3 integrin and a 56 kDa protein known as mobilferrin. In the cytosol of the absorptive cell, iron is associated with a 520-kDa complex known as paraferritin which contains integrin, mobilferrin, and flavin monooxygenase. This complex serves as a ferrireductase to reduce iron to the ferrous state so that it is available for formation of end products such as heme proteins. The large complex has other constituents, such as beta 2 microglobulin, whose functions remain to be delineated. We postulate that the basolateral membranes of absorptive cells possess both holo-transferrin and apotransferrin receptors that regulate the ingress and egress of cellular iron, respectively. Unlike absorptive cells, nonintestinal cells appear to possess three pathways for uptake of inorganic iron: (1) the classical transferrin-transferrin receptor pathway, (2) the transferrin-associated transferrin receptor independent pathway (TRIP), and (3) the transferrin-independent mobilferrin-integrin pathway (MIP) observed in intestinal absorptive cells. The TRIP is used when transferrin receptors become saturated at physiological concentrations of iron and transferrin. The MIP may only be used efficiently for mucosal uptake of iron and iron-overloaded individuals with fully saturated transferrin. Alternatively, it may facilitate iron uptake from the TRIP after degradation of transferrin near the surface of the cell. However, both transferrin-associated pathways donate iron to a common intracellular iron pathway for ferri-reduction and probably other functions.

Biological Transport↗
PubMed1997

The health of Canada's elderly population: current status and future implications.

The growing size of Canada's elderly population and its use of health care services has generated much discussion in policy circles and the popular press. With data from the National Population Health Survey, undertaken in 1994-95, the authors examine the health status of Canada's elderly population using 3 sets of measures: level of activity limitations, prevalence of chronic illnesses and self-assessment of overall health. They also analyse the utilization of physician and institutional services. The profile of this population the authors develop is in many respects not much different from that of the remaining adult population, until the age of 75. People aged 75 and over are much more likely than other adults to have health problems and use health care services. Also, elderly women living alone and with low income are identified as an especially vulnerable group who need access to medical and nonmedical services if they are to remain in the community. Using Statistics Canada projection data the authors discuss some aspects of the elderly population's health status in the future. Their look into the future raises issues about the preparedness of health care providers and our health care system to meet the challenges of tomorrow's elderly population.

Activities of Daily Living↗
PubMed1997

Structural characterization of human hemoglobin crosslinked by bis(3,5-dibromosalicyl) fumarate using mass spectrometric techniques.

Diaspirin crosslinked hemoglobin (DCLHb) was analyzed by mass spectrometric-based techniques to identify the protein modifications effected by the crosslinking reaction with bis(3,5-dibromosalicyl) fumarate. DCLHb consists of two principal components. These components were isolated by size-exclusion chromatography and identified by measurement of their molecular weight using electrospray mass spectrometry and subsequent peptide mass mapping and mass spectrometric sequence analysis of their individual digests. Three major RP-HPLC fractions were observed from the major hemoglobin in DCLHb. Their MWs matched the MW of heme, intact hemoglobin beta-chain, and two hemoglobin alpha-chains crosslinked by a fumarate moiety, respectively. The minor HPLC peaks of DCLHb were also separated, and characterized by mass spectrometric methods. These minor components revealed additional details of the structural nature of covalent modification of DCLHb.

Amino Acid Sequence↗
PubMed1997

The alternate iron transport pathway: mobilferrin and integrin in reticulocytes.

Iron transport in reticulocytes is known to occur via the well-described transferrin-receptor-endosome pathway. An alternative pathway for iron transport independent of transferrin has been postulated in reticulocytes and other cells. Transport of iron into reticulocytes from ferric citrate solutions was shown to be saturable and independent of transferrin. During transport of iron from ferric citrate, both cell surface integrins, and a soluble protein, mobilferrin, were labelled. This demonstrated that the reticulocyte transferrin independent pathway for iron transport involved integrins and mobilferrin similar to intestinal absorptive cells. This pathway would be expected to transport iron into cells under conditions of iron overload and was capable of providing iron for haemoglobin synthesis. Mobilferrin was also radiolabelled when radioiron labelled transferrin was incubated with reticulocytes and this occurred with a different time course than was observed following reticulocyte exposure to radiolabelled ferric citrate. This suggested that mobilferrin may serve as an intermediary in both pathways.

Animals↗
PubMed1996

Mobilferrin is an intermediate in iron transport between transferrin and hemoglobin in K562 cells.

Iron is bound to transferrin in the plasma. A specific receptor on the cell surface binds transferrin and internalizes transferrin and the iron in clathrin-coated pits. These invaginate to form vesicles which release iron to the cytoplasm. Inorganic iron can be transported by an alternative pathway from iron citrate, utilizing a cell surface integrin and a cytoplasmic protein mobilferrin. This article shows that the two pathways donate iron to mobilferrin which acts as an intermediate between the iron bound to transferrin and the incorporation of iron into hemoglobin. Mobilferrin is found associated with the transferrin containing vesicles, and becomes labeled with iron released from transferrin in the vesicles. Mobilferrin is also found in the cytoplasm where pulse-chase experiments show that it, in turn, releases iron to be used for the synthesis of hemoglobin.

Biological Transport, Active↗
PubMed1996

Paraferritin: a protein complex with ferrireductase activity is associated with iron absorption in rats.

Recent studies reported that iron salts were absorbed in the duodenum utilizing a pathway involving membrane-associated integrin and a cytosolic protein named mobilferrin. In addition, a large molecular weight cytoplasmic complex was labeled with radioiron during mucosal uptake of iron in the duodenum. The molecular mass of this protein was 520 000 daltons, slightly larger than ferritin. On denaturing SDS-PAGE, the purified protein complex appeared to consist of at least four polypeptides, closely associated with each other. This complex was called paraferritin because its hydrodynamic volume resembled ferritin. In the present work, antibody studies demonstrate the presence of integrin, mobilferrin, and flavin monooxygenase in the water-soluble complex. Biochemical studies demonstrate the presence of a NADPH-dependent flavin monooxygenase ferrireductase activity that reduces Fe(III) to Fe(II). Antibodies against either integrin or mobilferrin inhibit monooxygenase activity. Inhibition of monooxygenase activity decreases radioiron uptake by tissue culture intestinal cells. Thus, we postulated that paraferritin plays a role in the mucosal uptake and transport of inorganic iron in small intestinal absorptive cells and is a mechanism for both the internalization of integrin from membranes to cellular cytosol and the delivery of iron to cellular constituents in an appropriate redox state.

Animals↗
PubMed1995

Modelling migration flows of immigrant groups in Canada.

"In this paper, the authors briefly review the findings of an earlier study on the patterns of both regional and metropolitan redistribution of immigrant groups in Canada. Against this backdrop, a hierarchical model of migration for immigrant groups for the period 1981-86 is developed and estimated. The internal redistribution of immigrants through postarrival migration has continued to be focused on metropolitan areas in general and on Toronto, Vancouver, and Montreal in particular. The distribution of previous immigrants plays a significant role over and above that of economic circumstances both in retaining immigrants in a particular city and in attracting members of immigrant groups from other cities."

Americas↗
PubMed1995

Rapid, fully automated measurement of plasma homocyst(e)ine with the Abbott IMx analyzer.

We have developed a totally automated fluorescence polarization immunoassay for homocyst(e)ine with no pretreatment or chromatographic steps. Comparison with four well-established chromatographic methods yielded r values ranging from 0.980 to 0.997 and slopes from 1.030 to 1.493. Inter- and intraassay CVs ranged from 0.0% to 8.0% and from 0.0% to 6.4%, respectively. Imprecision (CV) of measuring six plasma samples on three instruments ranged from 6.3% to 10.2%. The assay was linear for plasma samples diluted with buffer from 0 to 8-fold. Mean recovery of homocysteine added to two plasma samples was 97.1% and 99.9%. The assay exhibited almost no cross-reactivity towards cysteine and methionine, and a batch of 20 samples can be processed in 60 min.

Autoanalysis↗