Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00080 (Leaf)
 21,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several T. brucei-subgroup strains isolated from game were investigated with the blood incubation infectivity test (BIIT) and in human volunteers. Original isolates and their clones derivatives were tested. In order to check the validity of the BIIT, volunteer tested clones were used under modified BIIT conditions. Inoculation of different trypanosome strains into volunteers yielded positive parasitaemia for original isolates from lion, hyaena, and Coke's hartebeest. Changing antibody titers during the course of infection in the volunteers were checked with the indirect fluorescent antibody test (IFT). The BIIT WAs reliable (consistently positive) for cloned T. b. rhodesiense. When testing T. b. brucei, the BIIT results depended on the number of incubated parasites and on the parasitaemia peak number the tested trypanosomes derived from. It was further shown that the in vivo part of the BIIT is actually essential for the complete neutralization of T. b. brucei induced by the action of human plasma. Tests with trypanosomes originating from experimentally mixed T. b. rhodesiense and brucei infections gave inconsistent results. On the other hand, pure populations mixed in vitro-prior to incubation for BIIT-revealed results depending on the proportion of the 2 species: up to 20% T. b. rhodesiense gave negative, higher concentrations consistently positive results.
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PMID:Identification of T. brucei-subgroup strains isolated from game. 0 83

Freeze-fracture electronmicroscopy has been used to examine the membrane ultrastructure of human red blood cells in the presence of inhibitors of chloride exchange. The extent of inhibition was correlated with a decrease of intramembrane particle density on the B-fracture face. Dimethylsulfoxide (DMSO) and glycerol, which markedly and reversibly reduced the intramembrane particle density, were shown to drastically and reversibly inhibit chloride self-exchange. DMSO was shown to be a noncompetitive inhibitor of chloride flux.
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PMID:Anion transport and membrane morphology. 0 77

The transport and phosphorylation of 2-deoxy-D-[3H]galactose in rabbit renal cortical cells was studied. 1. The uptake of 2-deoxy-galactose by cortical slices is associated with an appearance of both free and phosphorylated sugar in the cells. At 1 mM external sugar the cells establish a steady-state gradient of free 2-deoxy-galactose of 3.97 +/- 0.15 (23 animals). 2. The acid-labile sugar phosphate accumulated in the tissue has been identified by a combination of paper and radio-chromatography, as well as on the basis of some of its chemical properties, as 2-deoxy-D-galactose 1-phosphate. Ice-cold trichloroacetic acid produces a decomposition of this compound. 3. Increasing external pH (6-8) brings about a decrease in the steady-state levels of both free and phosphorylated sugar in slices. On the other hand, increasing pH activates the phosphorylation of 2-deoxy-D-galactose by a crude kinase in a tissue extract. 4. Sugar phosphate accumulated in the cells is dephosphorylated by the action of a Zn2+ -activated phosphatase. 5. The efflux of 2-deoxy-D-galactose from the cells is rather slow compared with that found for D-galactose. The efflux is associated with some dephosphorylation of cellular sugar phosphate, and some loss of 2-deoxy-galactose phosphate into the wash-out medium takes place. 6. An inhibition analysis of the uptake of 2-deoxy-D-galactose by the slices indicates that the transport site is shared by D-galactose. The following points of interaction between the sugar molecule and the carrier are identified: C1-OH, C3-OH and C4-OH (both axial) and C6-OH. A (pyranose) ring structure is also essential. A close packing between the substrate and the carrier in the vicinity of C2 is indicated. 7. The data suggest that the above transport system is localized predominantly at the antiluminal (basolateral) face of the renal tubular cells. While the detailed mechanism of the actual transport step (i.e. active transport of the free sugar, or by the action of a phosphotransferase) is still unclear, the data present evidence that both galactokinase and a Zn2+ -activated phosphatase participate in the maintenance of an intracellular steady state of the transported sugar.
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PMID:Transport and phosphorylation of 2-deoxy-D-galactase in renal cortical cells. 1 Sep 99

A levansucrase was demonstrated in the growth medium and in association with the cell surface of Actinomyces viscosus. The amount of enzyme produced relative to cell density is not significantly affected by the growth conditions. Sugar alcohols inhibit growth of the cells. The levansucrase hydrolyzes sucrose to produce free glucose and levan; some free fructose is also formed. There is no requirement for cofactors. The Km for sucrose is 12 mM. A variety of heavy metal ions and two disaccharides, lactose and cellobiose, inhibit the enzyme. The levansucrase was purified to homogeneity and has a specific activity of 90 micronmol of glucose release per min per mg. The enzyme has a molecular weight of 220,000 and is composed of subunits of molecular weight 80,000. The levan product contains both beta(2 leads to 1) and beta(2 leads to 6) linkages. The enzyme remains tightly bound to the levan product, resulting in the formation of high-molecular-weight polymer on the order of 10(8) daltons. The possible role of the levan and levansucrase of A. viscosus in the pathogenesis of periodontal disease is discussed.
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PMID:Levan and levansucrase of Actinomyces viscosus. 1 93

Stripped human hemoglobin was shown to have a high apparent zinc association constant of 1.3 X 10(7) M-1 with a stoichiometry of one zinc for every two hemes. The saturation of this site produces a dramatic 3.7-fold increase in the oxygen affinity. The effect of zinc on the oxygen affinity is interrelated with the interaction of 2,3-diphosphoglyceric acid (2,3-DPG) and hemoglobin. Thus, a smaller zinc effect is observed in the presence of added 2,3-DPG. Information about the location of the zinc-binding site responsible for the increased oxygen affinity has been obtained by comparing the binding of zinc to various hemoglobins. Blocking the beta93 sulfhydryl group decreases the apparent zinc association constant by an order of magnitude. The substitution of histidine-beta143 in hemoglobin Abruzzo [beta143 (H21) His leads to Arg] and hemoglobin Little Rock [beta143 (H21) His leads to Gln] decreases the apparent zinc association constant by two orders of magnitude. The substitution of histidine-beta143 by other amino acids and the reaction of the beta93 sulfhydryl group are known to produce dramatic increases in the oxygen affinity. The binding of zinc to one or both of these amino acids can, therefore, explain the zinc-induced increase in the oxygen affinity.
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PMID:Interaction of zinc and hemoglobin: binding of zinc and the oxygen affinity. 2 Sep 32

Freeze-etch electron microscopy of human erythrocytes from heparinized normal blood reveals membrane elevations. These elevations disappear at low pH values and reappear under normal pH conditions in vitro, both in the absence and the presence of plasma. This pH-dependent behaviour is discussed as an intrinsic membrane event.
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PMID:pH-dependent behaviour of erythrocyte membrane elevations. 2 5

1. pH-dependence of glycolysis has generally been ascribed to the effects of pH on the activities of glycolytic enzymes. The present study shows that sugar transport is pH-dependent in cultured Ehrlich ascites-tumour cells. 2. The rates of glucose consumption, of 3-O-methylglucose transport, and of 2-deoxyglucose transport and phosphorylation increased as linear functions of pH, as the pH of the cell culture medium was increased from 6.1 to 8.5. Transport of glucose, as measured in ATP-depleted cells, was pH-dependent to the same extent as transport of the non-metabolizable sugars. 3. Glucose consumption rates were about 8-fold higher at pH 8.5 than at pH 6.4. About 65-85% of glucose was converted into lactate. Sugar transport rates were 2.5-fold higher at pH 8.5 than at pH 6.3. 4. pH affected both simple diffusion and facilitated diffusion. pH effect was mainly on the Vmax. of 2-deoxyglucose uptake, and on the rapid-uptake phase of 3-O-methylglucose transport. 5. It was estimated that about 70% of the pH effect on the rates of glucose consumption may be due to the effect on sugar transport and the remainder to the effect on the activities of glycolytic enzymes.
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PMID:The pH-dependence of sugar-transport and glycolysis in cultured Ehrlich ascites-tumour cells. 3 Apr 54

The loss of biological activity upon heating or agitation of human interferons is markedly altered by changing their aqueous environment. Low pH significantly stabilizes liquid fibroblast interferon at 68 degrees C and 37 degrees C whereas chaotropic salts stabilize at 68 degrees C but not at 37 degrees C; this anomalous result may be due to reactivation of biological activity at the higher temperature. The concentration of extraneous proteins influences the apparent thermal stability at any temperature and pH; thus, interferon was not stable even at low pH at protein concentrations less than 5 microgram/ml. Solutions of partially purified fibroblast interferon can be inactivated by mechanical stress; the addition of proteins or nonionic detergents prevents such inactivation. Freeze-dried preparations show the greatest thermal stability. The use of high-temperature, accelerated storage tests makes it possible to predict the shelf-life of freeze-dried interferon.
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PMID:Thermal and vortical stability of purified human fibroblast interferon. 3 70

The Mg2+-dependent, K+-stimulated ATPase of microsomes from pig gastric mucosa has been studied in relation to observed active H+ transport into vesicular space. Uptake of fluorescent dyes (acridine orange and 9-aminoacridine) was used to monitor the generated pH gradient. Freeze-fracture electron microscopy showed that the vesicular gastric microsomes have an asymmetric distribution of intramembraneous particles (P-face was particulate; E-face was relatively smooth. Valinomycin stimulated both dye uptake and K+-ATPase (valinomycin-stimulated K+-ATPase); stimulation by valinomycin was due to increased K+ entry to some intravesicular activating site, which in turn depends upon the accompanying anion. Using the valinomycin-stimulated K+-ATPase and H+ accumulation as an index, the sequence for anion permeation was NO-3 greater than Br- greater than Cl- greater than I- greater than acetate approximately isethionate. When permeability to both K+ and H+ was increased (e.g using valinomycin plus a protonophore or nigericin), stimulation of K+-ATPase was much less dependent on the anion and the observed dissipation of the vesicular pH gradient was consistent with an 'uncoupling' of ATP hydrolysis from H+ accumulation. Thiocyanate interacts with valinomycin inhibiting the typical action of the K+ ionophore. But stimulation of ATPase activity was seen by adding 10 mM SCN- to membranes preincubated with valinomycin. From the relative activation of the valinomycin-stimulated K+-ATPase, it appears that SCN- is a very permeant anion which can be placed before NO-3 in the sequence of permeation. Valinomycin-stimulated ATPase and H+ uptake showed similar dependent correlations, including: dependence on [ATP] and [K+], pH optima, temperature activation, and selective inhibition by SH- or NH2-group reagents. These results are consistent with a pump-leak model for the gastric microsomal K+-ATPase which was simulated using Nernst-Planck conditions for passive pathways and simple kinetics for the pump. The pump is a K+/H+ exchange pump requiring K+ at an internal site. Rate of K+ entry would depend on permeability to K+ as well as the counterion, either (1) the anion to accompany K+ or (2) the H+ efflux path as an exchange ion. The former leads to net accumulation of H+ and anion, while the latter results in non-productive stimulation of ATP hydrolysis.
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PMID:Potassium-stimulated ATPase activity and hydrogen transport in gastric microsomal vesicles. 3 10

Freeze-fractured appearances of vesicle attachement sites (VAS) in presynaptic active zone were studied in the spinal cord of 4-aminopyridine (4-AP) treated and nembutalized rats. The VAS were classified into: type 1 containing no intramembranous particles, type 2 with particles around the edge of openings, type 3 containing several particles within the VAS. The application of 4-AP, which is known to enhance transmitter release, affected strikingly the total number of VAS (p less than 0.001) but not the proportion of the three types. The predominance of type 3 outside the active zone and its similarity to particle-loaded indentations possibly corresponding to coated vesicle formation, suggested that type 3 may represent endocytosis. It is likely that the remaining two types represent exocytosis.
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PMID:[Freeze fracture study of vesicle attachment sites during mediator liberation in spinal motoneuron synapses]. 3 10


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