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Biomedical subjects

E G Moore

Publications and source records attributed to E G Moore.

At least 37 records · Page 2Linked to original sources
PubMed1994

Concentration of serum amyloid P component in the CSF as a possible marker of cerebral amyloid deposits in Alzheimer's disease.

Serum amyloid P component (SAP) is a normal plasma protein produced in the liver and co-deposited with amyloid fibrils in all types of amyloidosis, including cerebral beta-protein amyloid deposits associated with Alzheimer's disease (AD). We have measured its concentration and those of alpha 2-macroglobulin, IgG and albumin in the CSF of 51 patients with AD and 50 healthy and disease control subjects. The mean levels of SAP were 12.8 ng/ml in AD and 8.5 ng/ml in controls (P < 0.0125); there was no difference in the levels of the other proteins studied. The observed concentrations of SAP were much lower than expected for a protein of molecular weight 254620. The difference between AD and controls suggests that the concentration of SAP in the CSF may be affected by the presence of cerebral amyloidosis.

Aged↗
PubMed1994

Alternate iron transport pathway. Mobilferrin and integrin in K562 cells.

A transferrin-independent iron transport system in cells containing transferrin receptors was described previously by several investigators. Prior studies did not identify the proteins involved in this alternate iron transport pathway. Using a human-derived erythroleukemia tissue culture line, iron-binding proteins were isolated from cytosol and cell membranes. The cytosol protein was soluble in 60% ammonium sulfate, had a molecular mass similar to mobilferrin (56 kDa), and reacted with anti-mobilferrin antibodies. The water-insoluble radiolabeled protein was solubilized with Nonidet P-40 and immunoprecipitated with monoclonal antibody against beta 3 human integrin. Pulse-chase studies suggested sequential passage of iron to integrin, mobilferrin, and ferritin, respectively. Thus, the alternate iron transport pathway contained proteins similar to those observed in intestinal cells which did not possess transferrin receptors on their absorptive surface. The alternate iron transport pathway is only partially shared with zinc and cadmium. Mobilferrin bound zinc and iron competitively, but the two metals were not transported competitively into K562 cells. Immunoprecipitates of integrin containing radiozinc were obtained with a monoclonal antibody against beta 1 human integrin. This suggested iron and zinc may utilize different integrins to passage the cell membrane.

Biological Transport↗
PubMed1994

Hereditary hemochromatosis: a prevalent disorder of iron metabolism with an elusive etiology.

Hereditary hemochromatosis is a prevalent inherited disorder with an estimated frequency of homozygosity of 0.2 to 0.45% in Caucasians. The disease is characterized by progressive iron overload until a massive accumulation of body iron occurs. Undetected, the disorder eventually can produce either cirrhosis, diabetes mellitus, cardiac disease, arthritis, or hepatocellular carcinoma or a combination of these manifestations. Early diagnosis and treatment prevents organ damage and normalizes life expectancy. Screening studies to detect hemochromatosis are most effectively accomplished by measurement of the serum iron and total iron binding capacity. Treatment is most effectively performed by frequent phlebotomy until body stores are empty and then 3 to 4 times yearly for life. The basic defect of hemochromatosis appears to increase iron absorption, decrease iron excretion, and produce preferential deposit of iron in hepatic parenchymal cells rather than Kupffer cells. The genetic abnormality of hemochromatosis is located on chromosome 6 in close association with the gene for HLA antigens. Recent speculation postulates that tumor necrosis factor may be involved in the etiology of this disease because of its location on chromosome 6 and its effect upon iron transport.

Family Health↗
PubMed1994

Rapid automated enzyme immunoassay of serum amyloid A.

Serum amyloid A (SAA), a sensitive acute-phase protein, is the precursor of AA fibrils in reactive amyloidosis. However, SAA is poorly immunogenic, and development and standardization of immunoassays of this protein have been difficult. We established an automated polyclonal/monoclonal microparticle capture enzyme immunoassay, standardized with the World Health Organization prospective reference standard for SAA. A stabilized concentrate of SAA was used for controls and calibrators. The assay range was 1-750 mg/L with CVs < 7% throughout. Plasma and serum gave identical results and no interferences were observed. Linear regression against radial immunodiffusion assay gave a slope of 1.04 (95% confidence interval 0.99-1.10), intercept of -9 mg/L (95% confidence interval -14-3), and residual SD (SEE) of 20 for samples containing < or = 200 mg/L (n = 173). In 105 apparently healthy adults the mean (SD) SAA concentration was 3.7 (3.6) mg/L, the median was 3.0 mg/L, and the range, 0.7-26.4 mg/L. In clinical acute-phase sera, values up to 2200 mg/L were seen. This method will facilitate measurement and investigation of SAA in clinical practice generally and in AA amyloidosis.

Acute-Phase Reaction↗
PubMed1993

Function of integrin in duodenal mucosal uptake of iron.

A mechanism for the absorption of inorganic iron in the small intestine is described in which integrins appear to play an important role in the passage of iron across microvillous membranes. Biochemical isolates from microvillous preparations of duodenum from rats dosed with radioiron showed radioactivity concentrated in integrins. The presence of integrins on mucosal surfaces of duodenal cells was confirmed by immunofluorescent microscopy using anti-integrin monoclonal antibodies. Immunoprecipitation methods were used to show that microvillous radioiron was precipitated with anti-integrin antibodies and that mobilferrin, a 56-Kd cytosol iron-binding protein, coprecipitated with integrins. We postulate from these data that the mucosal uptake of iron from the gut lumen is mediated via an integrin-mobilferrin pathway.

Animals↗
PubMed1993

Rat duodenal iron-binding protein mobilferrin is a homologue of calreticulin.

BACKGROUND: Mobilferrin is a water soluble 56-kilodalton protein isolated from human and rat duodenal mucosa. It binds iron and other transitional metals in vivo and in vitro and is postulated to play a role in their absorption and intracellular metabolism. The purpose of this study was to characterize mobilferrin. METHODS: Mobilferrin was characterized by identification of the N-terminal amino acid sequence, two-dimensional protein electrophoresis, and studies of mobilferrin and homologues using anti-mobilferrin antibody and competitive metal binding. RESULTS: The N-terminal amino acid sequence of mobilferrin was Asp-Pro-Ala-Ile-Tyr-Phe-Lys-Glu-Gln-Phe-Leu-Asp-Gly-Asp-Ala-Ser-Thr- and is a homologue of calreticulin (calregulin). The proteins had a similar molecular mass (56 kilodalton) and isoelectric point (4.7). Anti-mobilferrin antibodies react with calreticulin. Both proteins bind iron and calcium but have a greater affinity for iron. CONCLUSIONS: Mobilferrin and calreticulin are homologues that bind iron with greater affinity than calcium and other transitional metals. Competitive binding of metals by mobilferrin provides insight into the absorptive pathway shared by both essential and toxic transitional metals.

Amino Acid Sequence↗
PubMed1993

Regulation of iron absorption: proteins involved in duodenal mucosal uptake and transport.

Newly identified iron (Fe)-binding proteins isolated from both rat and human duodenal mucosa permit a better understanding of Fe absorption. Mucins bind Fe at acid pH to keep it soluble and available for absorption at the more alkaline pH of the duodenum; this explains the development of Fe deficiency in achlorhydric subjects. Integrin was identified on the surface of enterocytes in association with radioiron and is believed to facilitate the transfer of Fe through the microvillous membrane. Mobilferrin, a 56 kDa Fe-binding protein, was identified in enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrin in the apical cytoplasm of absorptive cells. We postulate it accepts dietary Fe from integrin and acts as the shuttle protein from Fe in the cytoplasm. Since Fe in enterocytes remains in equilibrium with body stores, we postulate mucosal Fe uptake is regulated by the number of Fe-binding sites either occupied or unoccupied by Fe on mobilferrin. Fe repletion of enterocytes from body stores is probably accomplished via transferrin receptors on the basal membranes of enterocytes. Increased transfer of Fe from blood into absorptive enterocytes occurs in Fe-replete animals to inhibit mucosal uptake of dietary Fe. Little transfer of Fe from plasma to enterocytes occurs in Fe deficiency. Enhanced mucosal transfer into the body occurs with increased body need for Fe. The exact mechanism for mucosal transfer of Fe into the plasma has not been defined but may also be mediated by an integrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Newly identified iron-binding protein in human duodenal mucosa.

Studies were undertaken using human duodenal mucosa to determine whether it contained a counterpart to a newly identified iron-binding protein recently isolated from rat duodenum and named mobilferrin. Water-soluble homogenates were prepared from duodena of patients undergoing surgery for pancreatic carcinoma. An iron-binding protein with an approximate molecular mass of 56 Kd was purified to homogeneity using 60% ammonium sulfate and serial chromatographic steps. The protein was biochemically and immunologically distinct from transferrin and ferritin, and competitively bound to zinc, cobalt, and lead. Each molecule bound one molecule of iron with a kd of 8.9 x 10(-5). Human isolates reacted in an enzyme-linked immunosorbent assay with a polyclonal antibody raised in rabbits against a similar duodenal protein isolated from rat duodenum. It is postulated that mobilferrin plays a significant role in the absorption of iron and other metals and may explain partially the competition between certain metals for absorption in the small intestine.

Ammonium Sulfate↗
PubMed1991

A role for mucin in the absorption of inorganic iron and other metal cations. A study in rats.

The steps involved in iron absorption are poorly understood. Although transferrin and ferritin are water soluble, most radioiron in gut homogenates after an intraluminal dose of radioiron is recovered in water-insoluble precipitates. Most radioiron in the precipitates was insoluble in detergents and organic solvents and was characterized as mucins. These isolates bound iron in vitro with a Kd of 9.09 x 10(-5). Similar iron binding was observed with commercial mucins. Iron binding to mucin occurred at acid pH and maintained the iron available for absorption with alkalinization. Similar pH-dependent binding to mucin was observed with zinc, cobalt, and lead. Iron competitively inhibited binding of these metals to mucin. However, iron chelates of ascorbate, fructose, and histidine donated iron to mucin at neutral pH. These data provided a role for gastric HCl and intestinal mucin in absorption of iron and metal cations and partial explanation of the competition for absorption between certain metals from the gut lumen. It is postulated that intestinal mucin delivers inorganic iron to intestinal absorptive cells in an acceptable form for absorption.

Animals↗
PubMed1990

A newly identified iron binding protein in duodenal mucosa of rats. Purification and characterization of mobilferrin.

An iron binding protein with an approximate molecular mass of 56,000 daltons was purified to homogeneity from homogenates of rat duodenal mucosa. The protein was biochemically and immunologically distinct from transferrin and ferritin and competitively bound cobalt, copper, zinc, and lead. Each molecule bound one molecule of iron with a Kd of 9 X 10(-5). Dissociation of iron and the protein was accelerated at acid pH. Using an immunogold method, the protein was identified in the apical cytoplasm of proximal small intestinal cells and was not observed elsewhere in the intestinal mucosa and in other body organs. It was named mobilferrin from its city of origin and to differentiate it from other previously identified iron binding proteins.

Amino Acids↗
PubMed1989

Components of change in the spatial distribution of the elderly population in Ontario, 1976-1986.

"Using data from the 1976, 1981, and 1986 [Canadian] Censuses for Ontario, components of change in the elderly population are obtained by cohort survival methods. The significance of rapid metropolitan growth of the elderly compared with the slow growth of the rural elderly is highlighted, while intra-county distributional shifts in the elderly population raise important questions for the next decade." (SUMMARY IN FRE)

Adult↗
PubMed1984

Antibody to immunoselected L-cell antigens mimics stimulating activity of antibody to whole L cells.

A heterogeneous IgG antibody raised in rabbits in response to injections of whole L cells was used to identify and select relevant antigens in a nonionic detergent extract of L cells prelabeled with [35S]methionine by means of immunoprecipitation and immunoaffinity chromatography. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the immunoprecipitate and immunoeluate contained far fewer protein bands than the whole cell extract but selectively retained a 42,000-MW protein species. In response to injections of the immunoprecipitate, rabbits produced a new antiserum which reacted predominantly with the 42,000-MW protein when reacted with L-cell proteins separated by sodium dodecyl sulfate-gel electrophoresis and transferred to nitrocellulose paper by the Western blot technique. The new antiserum (raised to the immunoprecipitate) and the original antiserum (raised to whole cells) were equipotent in stimulating calcium transport, phospholipid metabolism, and DNA synthesis in L cells. Binding of the IgG fractions of the two antisera displayed identical high affinity binding to L-cell surface antigens, with the same average association constant of 1.5 X 10(6) M-1. These studies have shown that an antiserum raised to whole L cells has a much narrower reactive spectrum with L-cell membrane antigens than might be imagined and has identified a 42,000-MW membrane protein as an important immunogen which itself elicits a potent immune response resulting in an antibody capable of mimicking the cell stimulatory properties of the original antiserum.

Animals↗
PubMed1984

Correlation between covalent attachment of C3 and calcium uptake in antibody-stimulated L cells.

The nature of C3 binding to cell surfaces was examined in L cells treated with antibody and complement, immunological reagents which we have previously shown to be capable of producing stimulation of several important cellular processes. In the presence of serums containing C3 and under experimental conditions where complement activation could take place, selective binding of C3 to antibody treated L cells was observed (maximum 1.1 X 10(6) C3 molecules per cell). Under similar conditions there was a C3 dependent increased calcium uptake (3.4 pmol) by antibody treated cells. Purified C3 was able to selectively restore C3 binding to cells treated with serum depleted of C3 through C9. C7-deficient serum was almost as good a source of activated C3 as its normal serum counterpart. Strong chemical nucleophiles such as salicylhydroxamic acid, which are capable of covalently coupling to the labile internal thiolester of C3, prevented the binding of C3 to cells. We conclude that C3 is covalently bound to antibody and complement treated L cells, possibly serving as an important signal in subsequent enhancement of phospholipid metabolism, DNA synthesis, and cell growth.

Animals↗
PubMed1982

Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection.

We studied the incidence of primary and recurrent cytomegalovirus infection in 3712 pregnant women--2698 of middle to high income and 1014 of low income--to determine whether there were differences in the effects on the fetus. In the higher-income group, 1203 women (45 per cent) did not have antibodies to cytomegalovirus and were therefore susceptible to primary infection, as compared with 179 women (18 per cent) of low income. Congenital infection occurred more often (1.6 vs. 0.6 per cent) in infants in the low-income group. In this group it was associated with recurrent maternal infection more often (in 82 per cent) than with primary maternal infection, whereas in the upper-income group, it was associated with primary maternal infection in half the cases. Altogether, there were 32 cases of congenital cytomegalovirus infection - 16 in each group. Whereas primary maternal infection resulted in fetal infection in only half the cases, it was more likely to ge associated with clinically apparent disease than was recurrent infection. When these cases were combined with 28 cases of congenital infection retrospectively identified at other prenatal clinics, five of 33 infected infants born after primary maternal infection had clinically apparent disease, as compared with none of 27 born after recurrent maternal infection. We conclude that congenital cytomegalovirus infection resulting from primary maternal infection is more likely to be serious than that resulting from recurrent infection, and is more likely to occur in upper socioeconomic groups.

Adult↗