Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune guinea pig lymph node cells were fractionated on Ig anti-Ig or HSA anti-HSA affinity columns or on plastic surface in medium containing carbonyl iron. These techniques selectively removed B lymphocytes, K lymphocytes or adherent cells. The residual cells (Fc receptor-negative T lymphocytes) responded to soluble antigen in vitro in the same way or even better compared with nonfractionated cells. In addition, there was no indication that antigen-antibody complexes were superior to antigen in triggering lymph node cells or purified lymph code T lymphocytes into DNA synthesis. The results obtained suggested that memory T lymphocytes can be stimulated by antigen autonomously.
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PMID:Lymphocyte proliferation in vitro induced by soluble protein antigens. II. Cellular requirements. 108 85

Hydroxy-urea bearing albumin microspheres were prepared using the polymer dispersion method. Glycerol was used successfully in place of water as an internal phase of w/o emulsion, to prepare HSA based albumin microspheres. Silicone coated magnetite of nanometeric size was incorporated in the drug bearing microspheres. The process variables which could affect the physical characteristics with respect to in vitro and in vivo performance of the prepared microspheres were studied. The in vitro release of the drug from the microspheres followed a linear relationship when commulative per cent drug release was plotted against square root of time. Microspheres of average size 1-4 microns were studied for in vivo distribution and localization. It was established that 67 per cent of the drug enveloped in magnetic albumin microspheres could be localized in a rat tail target segment, on applying an external magnetic field of strength 8000 Oe. A remarkable stabilization of hydroxy urea in the prepared microspheres was recorded when t10% drug degradation was compared with the albumin microspheres prepared by a conventional emulsion polymerization method using water as an internal phase.
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PMID:Hydroxy-urea bearing albumin microspheres--preparation, characterization and evaluation. 188 Jun 96

Because ibuprofen protects from septic lung injury, we studied the effect of ibuprofen in oxidant lung injury from phosgene. Lungs from rabbits exposed to 2,000 ppm-min phosgene were perfused with Krebs-Henseleit buffer at 50 ml/min for 60 min. Phosgene caused no increase in lung generation of cyclooxygenase metabolites and no elevation in pulmonary arterial pressure, but markedly increased transvascular fluid flux (delta W = 31 +/- 5 phosgene vs. 8 +/- 1 g unexposed, P less than 0.001), permeability to albumin (125I-HSA) lung leak index 0.274 +/- 0.035 phosgene vs. 0.019 +/- 0.001 unexposed, P less than 0.01; 125I-HSA lavage leak index 0.352 +/- 0.073 phosgene vs. 0.008 +/- 0.001 unexposed, P less than 0.01), and lung malondialdehyde (50 +/- 7 phosgene vs. 24 +/- 0.7 mumol/g dry lung unexposed, P less than 0.01). Ibuprofen protected lungs from phosgene (delta W = 10 +/- 2 g; lung leak index 0.095 +/- 0.013; lavage leak index 0.052 +/- 0.013; and malondialdehyde 16 +/- 3 mumol/g dry lung, P less than 0.01). Because iron-treated ibuprofen failed to protect, we studied the effect of ibuprofen in several iron-mediated reactions in vitro. Ibuprofen attenuated generation of .OH by a Fenton reaction and peroxidation of arachidonic acid by FeCl3 and ascorbate. Ibuprofen also formed iron chelates that lack the free coordination site required for iron to be reactive. Thus, ibuprofen may prevent iron-mediated generation of oxidants or iron-mediated lipid peroxidation after phosgene exposure. This suggests a new mechanism for ibuprofen's action.
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PMID:Ibuprofen prevents oxidant lung injury and in vitro lipid peroxidation by chelating iron. 217 23

Lactoferrin (LTF), which is the major iron-binding protein in milk and physiological fluids, belongs to the transferrin family. We report here the sequence of a caprine LTF cDNA, 2411 bp in length, encoding the pre-protein (709 amino acid residues). Sequence comparisons reveal that structural features, including iron-binding sites, cysteine residues involved in disulphide bonds are remarkably conserved between LTF proteins from various species. Of the 5 potential glycosylation sites identified, only one site appears to be conserved between artiodactyls, rodents and humans. Using a somatic cell hybrid panel, the LTF locus was assigned to the bovine U12 syntenic group. This assignment and the localization of the LTF gene on bovine chromosome 22 (BTA 22) by Schwerin et al. (1) using fluorescent in situ hybridization achieves an additional analogy between a synteny group and a chromosome in cattle. Since serum transferrin (STF) had been previously mapped on BTA 1, in cattle LTF and STF loci are not localized on the same chromosome, conversely to the situation observed in humans (HSA 3) and mice (MMU 9).
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PMID:Characterization of the goat lactoferrin cDNA: assignment of the relevant locus to bovine U12 synteny group. 809 48

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the transferrin-USPIO obtained was investigated in vivo in experimental SMT/2A tumor-bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R1 = 23.6 and R2 = 52.1 liter/mmol.s (0.47 T). Bound transferrin was 280 micrograms/mg of iron. Pharmacokinetic investigations revealed a half-life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25-55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA-USPIO) showed a change of only 10% (range 5-15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin-mediated endocytosis allows in vivo detection of tumors by MR imaging.
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PMID:Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in vivo by using transferrin receptor pathways. 970 5

The effect of bezafibrate (BZF) and clofibrate (CF), two therapeutic drugs displaying anticoagulant and antihyperlipoproteinemic activities, on the EPR-spectroscopic properties of ferrous nitrosylated heme-human serum albumin (HSA-heme-NO) has been investigated. In the absence of BZF and CF, HSA-heme-NO is a five-coordinate heme-iron system, characterised by an X-band EPR spectrum with a three-line splitting in the high magnetic field region. Addition of BZF and CF to HSA-heme-NO induced the transition towards a six-coordinate heme-iron species characterised by an X-band EPR spectrum with an axial geometry. These data indicate that HSA-heme-NO is a five-coordinate heme-iron system, BZF and CF acting as allosteric effectors, and show that the primary heme binding site and the CF cleft of HSA are conformationally-linked, regardless of their different location.
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PMID:Effect of bezafibrate and clofibrate on the heme-iron geometry of ferrous nitrosylated heme-human serum albumin: an EPR study. 1137 93

Hemalbumin [i.e., Fe(III)-protoporphyrin IX-human serum albumin; Fe(III)heme-HSA] is an important intermediate in the recovery of heme iron following hemolysis. Relaxometric data are consistent with the occurrence of a hexacoordinated high-spin Fe(III) center with no water in the inner coordination sphere. The relatively high relaxation enhancement observed for an aqueous solution of Fe(III)heme-HSA (r1p=4.8 mM(-1)s(-1) at 20 MHz, pH 7, and 25 C) is ascribed to the occurrence of a strong contribution from water molecules in the second coordination sphere. Structural analysis of the putative binding region has been performed by a Monte Carlo simulated annealing procedure, which allowed us to identify His105 and Tyr148 as axial ligands. The role of a tyrosinate as the sixth Fe(III)heme ligand is supported by the pH-dependent analysis. Interestingly, when Fe(III) is replaced by Mn(III), the occurrence of a fast exchanging water molecule at pH values close to neutrality is detected. As the pH is increased, the Mn(III) containing system behaves analogously to Fe(III)heme-HSA. At higher pH, the phenolate ligand is eventually displaced by OH- from both Fe(III) and Mn(III) centers. Support for the proposed bonding scheme has been gained also from competitive binding assays for the sixth coordination site by fluoride, azide, and imidazole ligands.
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PMID:Relaxometric characterization of human hemalbumin. 1147 28

The widespread presence of pathogenic bacteria is a cause of permanent demand for investigating the properties of antimicrobial agents. The chemical basis of several toxic effects induced by antibiotics still remains unclear. Aminoglycosides, highly ototoxic and nephrotoxic drugs, are capable of copper(II) ions chelating. In this study we established the affinity of kanamycin A towards copper(II), in contrast with other metal ions: iron(III), nickel(II), cobalt(II) and zinc(II) by means of potentiometry. Circular dichroism spectroscopy was applied to monitor the competition of copper(II) partition between kanamycin A and human serum albumin. We show, that the drug is able to digest Cu(II) ions from HSA to some extent and comparing the stability constants for metal and antibiotic with those, obtained for the N-terminal Asp-Ala-His-Lys (DAHK) sequence, which constitutes a copper(II) binding domain within albumin, we demonstrate that the Cu(II)-kanamycin A complex formation is possible also in blood plasma. Bioassays and immunoassay were used to find out the possibility of Cu(II)-kanamycin A complexes to induce cytokines: tumor necrosis factor (TNF), interferon (IFN) and interleukin-10 (IL-10) in human peripheral blood leukocytes. The effect on the cytokines release was dose and time dependent and the interdependence between IL-10 and TNF stimulation was found. We report that Cu(II)-aminoglycoside systems can act as moderate inducers of TNF-alpha, IFN-alpha/beta and IL-10 released from human leukocytes. We have also found that these complexes are non-toxic for human A549 cells.
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PMID:Preferences of kanamycin A towards copper(II). Effect of the resulting complexes on immunological mediators production by human leukocytes. 1472 5

Complexing an iron protoporphyrin IX into a genetically engineered heme pocket of recombinant human serum albumin (rHSA) generates an artificial hemoprotein, which can bind O2 in much the same way as hemoglobin (Hb). We previously demonstrated a pair of mutations that are required to enable the prosthetic heme group to bind O2 reversibly: (i) Ile-142-->His, which is axially coordinated to the central Fe2+ ion of the heme, and (ii) Tyr-161-->Phe or Leu, which makes the sixth coordinate position available for ligand interactions [I142H/Y161F (HF) or I142H/Y161L (HL)]. Here we describe additional new mutations designed to manipulate the architecture of the heme pocket in rHSA-heme complexes by specifically altering distal amino acids. We show that introduction of a third mutation on the distal side of the heme (at position Leu-185, Leu-182, or Arg-186) can modulate the O2 binding equilibrium. The coordination structures and ligand (O2 and CO) binding properties of nine rHSA(triple mutant)-heme complexes have been physicochemically and kinetically characterized. Several substitutions were severely detrimental to O2 binding: for example, Gln-185, His-185, and His-182 all generated a weak six-coordinate heme, while the rHSA(HF/R186H)-heme complex possessed a typical bis-histidyl hemochrome that was immediately autoxidized by O2. In marked contrast, HSA(HL/L185N)-heme showed very high O2 binding affinity (P1/2O2 1 Torr, 22 degrees C), which is 18-fold greater than that of the original double mutant rHSA(HL)-heme and very close to the affinities exhibited by myoglobin and the high-affinity form of Hb. Introduction of Asn at position 185 enhances O2 binding primarily by reducing the O2 dissociation rate constant. Replacement of polar Arg-186 with Leu or Phe increased the hydrophobicity of the distal environment, yielded a complex with reduced O2 binding affinity (P1/2O2 9-10 Torr, 22 degrees C), which nevertheless is almost the same as that of human red blood cells and therefore better tuned to a role in O2 transport.
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PMID:Genetic engineering of the heme pocket in human serum albumin: modulation of O2 binding of iron protoporphyrin IX by variation of distal amino acids. 1770 94

Transition metal-based drugs exhibit high affinity to the soft donors of human serum proteins, especially of the high-abundance protein HSA and of transferrin (Tf), whereas Ga(III) salts are known to bind to Tf and other iron-containing metalloproteins, thereby interfering with the iron metabolism. Herein, the utilization of CE-MS methods for studying the binding behavior of a therapeutic gallium nitrate formulation and the anticancer drug candidate Tris(8-oxyquinolinato)gallium(III) to Tf and HSA under simulated physiological conditions is described. Both the Ga(III) salt and the complex were found to bind to Tf exclusively in the presence of carbonate, however, at different kinetics and to a different extent. Fe(III) induces the release of the Ga ions due to the higher affinity constant and also prevents the Ga(III) species from accessing the iron-binding pockets of Tf. In contrast, only low affinity to HSA was observed and even when present at ca. 20-fold excess, the majority of the Ga was attached to Tf.
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PMID:The serum protein binding of pharmacologically active gallium(III) compounds assessed by hyphenated CE-MS techniques. 1962 74


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