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E B Cunningham

Publications and source records attributed to E B Cunningham.

15 recordsLinked to original sources
PubMed1999

An inositolphosphate-binding immunophilin, IPBP12.

A novel inositolphosphate-binding protein has been identified and shown to be an immunophilin. This protein, which was isolated from human erythrocyte membranes and from K562 (human erythroleukemia) cell membranes, has robust peptidylprolyl cis-trans isomerase activity that is strongly inhibited by nanomolar concentrations of FK506 or rapamycin, indicating a member of the FKBP (FK506-binding protein) class. However, unlike the cytosolic FKBP12, the isomerase activity of this membrane-associated immunophilin is strongly inhibited by nanomolar concentrations of inositol 1,4, 5-trisphosphate (IP(3)), inositol 1,3,4,5-tetrakisphosphate (IP(4)), and phosphatidylinositol 4- and 4,5-phosphates, which are suggested to be physiological ligands. The demonstration of a single 12-kD protein that binds both IP(4) or IP(3) and anti-FKBP12 provides strong support for the inositolphosphate-binding immunophilin having an apparent mass of 12 kD, and it is suggested that the protein might be called IPBP12 for 12-kD inositol phosphate binding protein. When an internal tryptic peptide derived from IPBP12 was sequenced, a sequence also present in human cytokeratin 10 was identified, suggesting a cytoskeletal localization for the immunophilin. While purifying IPBP12, it was found that it is immunoprecipitated with specific proteins that include a protein kinase and a phosphoprotein phosphatase. The latter is indicated to be phosphoprotein phosphatase 2A (PP-2A). It is suggested that immunophilins promote the assembly of multiprotein complexes that often include a protein kinase or a phosphoprotein phosphatase or both.

Amino Acid Sequence↗
PubMed1995

The human erythrocyte membrane contains a novel 12-kDa inositolphosphate-binding protein that is an immunophilin.

A 12-kDa inositolphosphate-binding protein has been identified as a component of the human erythrocyte membrane. Its robust peptidylprolyl cis-trans isomerase activity that is strongly inhibited by the immunosuppressant drugs FK506 and rapamycin indicates that it is an immunophilin belonging to the FKBP class. The finding that its peptidylprolyl cis-trans isomerase activity is also strongly inhibited by nanomolar concentrations of the second messengers inositol 1,4,5-trisphosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4) suggests that IP3 and IP4 could be physiological ligands for this membrane-associated immunophilin.

Amino Acid Isomerases↗
PubMed1993

Comparison of the Seradyn Color Vue passive agglutination test and complement fixation for detection of Mycoplasma pneumoniae antibodies.

We compared traditional complement fixation (CF) with a new passive agglutination method, the Seradyn Color Vue (SCV) test (Seradyn, Indianapolis, Ind.), for detection of Mycoplasma pneumoniae antibodies in 170 stored serum samples. The SCV test was 90% sensitive in identifying as positive 27 of 30 CF high-titer (> or = 1:64) serum samples and 100% specific in identifying as negative 134 of 134 CF low-titer (< or = 1:32) or negative (< 1:8) serum samples. The SCV test was technically undemanding, and it required no expensive equipment.

Agglutination Tests↗
PubMed1991

A 20 kDa erythrocyte membrane phosphoprotein.

A small (approximately 20 kDa) protein associated with the human erythrocyte membrane undergoes phosphorylation that is potentiated by the addition of phosphatidylinositol. It is indicated that phosphatidylinositol 4.5-bisphosphate, generated in situ during the protein phosphorylation reaction. is the effective agent. Phosphorylation of the small protein is also potentiated when isolated membranes are exposed to conditions that promote the phosphorylation of the phosphatidylinositols. It is suggested that the 20 kDa membrane protein participates in biochemical signaling in the erythrocyte.

Erythrocyte Membrane↗
PubMed1991

A p-nitrophenylphosphatase activity associated with the human erythrocyte membrane.

A p-nitrophenylphosphatase activity has been identified as a component of the human erythrocyte membrane. This activity is distinct from that associated with the cell's Na(+)+K(+)-dependent ATPase, Ca(2+)-dependent ATPase, or spectrin phosphatase. The activity described here is stimulated by Mn2+ but not by Ca2+ with or without calmodulin. A potential erythrocyte membrane substrate for this activity is a 95 kDa phosphoprotein that can be shown to undergo Mn(2+)-stimulated but not Mg(2+)-stimulated dephosphorylation.

4-Nitrophenylphosphatase↗
PubMed1991

Variability in commercial histoplasma complement fixation antigens.

Using Immuno-Mycologics (IMMY; Norman, Okla.) histoplasmal yeast (HY) and mycelial (HM) antibody complement fixation test antigens, we retested 1,386 samples that were initially tested with Meridian Diagnostics, Inc. (Cincinnati, Ohio), antigens. Histoplasma antibody was identified (greater than or equal to 1:16) in 20% of HY and 5% of HM samples reported to have titers of less than 1:8 with Meridian reagents. IMMY titers were at least fourfold higher than Meridian titers in 39% of HY and 54% of HM samples that initially had titers of greater than or equal to 1:8 with Meridian antigens. Because 30 of 58 (52%) samples from confirmed cases of histoplasmosis yielded negative results with Meridian antigens and positive results upon retesting with IMMY antigens, we concluded that the Meridian antigens had less reactivity with human histoplasmal antibody.

Antigens, Fungal↗
PubMed1989

Evaluation of four methods for cytomegalovirus antibody detection for use by a bone marrow transplantation service.

Four methods, latex agglutination, indirect fluorescent antibody, enzyme immunoassay, and complement fixation, were compared for cytomegalovirus antibody screening and for pre- and posttransplant determinations on bone marrow transplant recipients. Latex agglutination was most sensitive (98%) and specific (97%) for screening and pretransplant determinations and was quickest and easiest to perform. In posttransplant sera from allogeneic bone marrow transplant recipients, all methods except complement fixation detected cytomegalovirus antibody from therapeutically administered globulin preparations; this made it difficult to determine the significance of changes in cytomegalovirus antibody titer.

Antibodies, Viral↗
PubMed1984

Effect of tellurium position on the myocardial uptake of radioiodinated 18-iodotellura-17-octadecenoic acid analogues.

The effect of tellurium (Te) position on myocardial specificity and retention of fatty acids in which radioiodide is stabilized as a trans-(E)-vinyl iodide has been evaluated in rats. Five analogues of 18-iodo-17-octadecenoic acid (ICH = CH-R-Te-R'-COOH) with Te at positions 5, 7, 9, 11, and 13 were prepared by coupling of a trans-diiodoalkene (ICH = CH-R-I) with the requisite sodium [(alkoxycarbonyl)alkyl]telluride substrate (NaTe-R'-COOR"; R" = Me or Et), followed by basic hydrolysis. By varying R and R', a series of analogues with a chain length of 18 carbon atoms was prepared. The telluride substrates were generated in situ by NaBH4 reduction of the corresponding ditellurides, and the diiodoalkenes were prepared by sodium iodide-chloramine-T treatment of the corresponding vinylboronic acids [(HO)2BCH = CH-R-I)]. The vinylboronic acids were prepared by treatment of the terminal acetylenes (HC identical to C-R-I), synthesized from commercially available materials, with catecholborane. All new compounds were analyzed by TLC, NMR, MS, and elemental analyses. The 125I analogues [(E)-125ICH = CH-R-Te-R'-COOH] were prepared in the same manner and evaluated in rats (four per group). Heart uptake and retention were dependent upon the Te position. The analogue with Te at position 5 showed the most pronounced (5-min values) heart uptake (3.7-4.1 dose/g), myocardial retention, and heart/blood ratios (37:1) and is a candidate for radiolabeling with 123I and further evaluation as a myocardial imaging agent.

Animals↗
PubMed1983

Modulation of the activity of the (Ca2+ + Mg2+)-dependent adenosine triphosphatase of the human erythrocyte.

We previously reported that the activity of the (Ca2+ + Mg2+)-dependent adenosine triphosphatase (ATPase) of the human erythrocyte membrane is inhibited by micromolar or nanomolar concentrations of cyclic AMP. Our further studies have now indicated that the inhibition of (Ca2+ + Mg2+)-dependent phosphohydrolase activity requires the participation of a membrane-associated cyclic AMP-dependent protein kinase and a membrane-associated protein substrate that is distinct from the ATPase itself. We have furthermore, identified a 20 kDa membrane protein which undergoes phosphorylation that is promoted by micromolar, but not millimolar, concentrations of cyclic AMP and which, when phosphorylated, undergoes dephosphorylation that is promoted by Ca2+. We suggest that this membrane component can participate in the modulation of the activity of the (Ca2+ + Mg2+)-dependent ATPase of the human erythrocyte.

Ca(2+) Mg(2+)-ATPase↗
PubMed1983

Potential cerebral perfusion agents: synthesis and evaluation of a radioiodinated vinylalkylbarbituric acid analogue.

A new iodinated barbiturate has been prepared. Treatment of 5-chloropentyne and propargyl bromide with diethyl 2-ethyl-2-sodiomalonate (DESM) provided diethyl 2-ethyl-2-(1-pentyn-5-yl)malonate (3) and diethyl 2-ethyl-2-propargylmalonate (4), respectively. Similar condensation of DESM with (E)-(5-iodo-1-penten-1-yl)boronic acid (9) or the reaction of catecholborane with 3 provided diethyl (E)-2-ethyl-2-(1-borono-1-penten-5-yl)malonate (8). The direct sodium iodide-chloramine-T iodination of 8 or the treatment of (E)-1,5-diiodo-1-pentene (10) with DESM provided diethyl (E)-2-ethyl-2-(1-iodo-1-penten-5-yl)malonate (11). The condensation of functionalized malonates 3, 4, and 11 with urea in the presence of a base provided the corresponding barbiturates, 5-ethyl-5-(1-pentyn-5-yl)-(5), 5-ethyl-5-propargyl- (6), and (E)-5-ethyl-5-(1-iodo-1-penten-5-yl)barbituric acid (12), respectively. (E)-6-(Ethoxycarbonyl)-1-iodo-1-octene-6-carboxylic acid (13) was isolated as the hydrolytic byproduct of 11. Compound 13 decarboxylated under vacuum to provide ethyl (E)-1-iodo-1-octene-6-carboxylate (14). The 125I-labeled congeners of 12 and 13 were synthesized in the same manner and evaluated in rats. The barbiturate 12 exhibited significant brain uptake (approximately 1% dose after 5 min), demonstrating that iodinated barbiturates freely cross the intact blood-brain barrier.

Animals↗
PubMed1980

The influence of adenosine 3',5'-monophosphate upon the activity of the membrane-associated (Ca+ + Mg2+)-dependent adenosine triphosphatase of the human erythrocyte.

The phosphohydrolase activity of the membrane-associated (Ca2+ + Mg2+)-dependent adenosine triphosphatase (ATPase) of the human erythrocyte can be inhibited by micromolar of nanomolar concentrations of cyclic AMP. Millimolar concentrations of cyclic AMP are less effective. The inhibitory effect of cyclic AMP is potentiated in the presence of the phosphodiesterase inhibitor, theophylline.

Ca(2+) Mg(2+)-ATPase↗
PubMed1979

An adenosine 3':5'-monophosphate-dependent protein kinase from the human erythrocyte membrane. Purification and characterization.

An adenosine 3':5'-monophosphate-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) has been isolated from the human erythrocyte memebrane and the phosphotransferase activity exhibited by this enzyme has been purified 800-fold. In concentrated solutions, the membrane-derived protein kinase undergoes aggregation with a concomitant loss in observed phosphotransferase activity. This loss of activity can be restored by means of inducing deaggregation. The phosphotransferase activity of the protein kinase is virtually obliterated in the presence of high (300 mM) concentrations of sodium chloride. This effect is also reversible. The pH optimum for the phosphotransferase reaction that is catalyzed by the membrane-derived protein kinase is approximately 8. Micromolar concentrations of cAMP are optimal with respect to promoting the phosphotransferase reaction. Initial velocity and product inhibition studies were conducted on the cAMP-independent protein kinase derived from the cAMP-dependent enzyme. These studies indicate that the phosphotransferase reaction proceeds by a sequential kinetic mechanism.

Cyclic AMP↗