Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Albumin was isolated from pooled fetal serum obtained at normal delivery at term and from pooled adult plasma. Albumin isolation was carried out by means of PEG precipitation followed by ion exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (6 nM) to albumin (40 g/l) was measured by equilibrium dialysis at 37 degrees C. The unbound fraction (mean +/- SD) for fetal and adult albumin of diazepam was 1.86 +/- 0.24 and 1.82 +/- 0.15% (NS), that of digitoxin was 3.18 +/- 0.27 and 3.36 +/- 0.04% (NS) and that of salicylic acid was 11.65 +/- 0.99 and 9.47 +/- 0.75% (p less than 0.05), respectively. With both fetal and adult albumin, a single class of binding sites was observed for diazepam and digitoxin, whereas two classes of binding sites were observed for salicylic acid. The number of binding sites (n, moles of drug per mole of albumin) for fetal and adult albumin was 0.83 and 1.02 for diazepam and 0.014 and 0.018 for digitoxin, respectively. For salicylic acid, n was 1.45 (fetal albumin) and 1.55 (adult albumin) for the higher affinity site, and 3.06 (fetal albumin) and 3.27 (adult albumin) for the lower affinity site. The association constant (Ka, M-1) for diazepam was 1.36 x 10(5) (fetal albumin) and 1.00 x 10(5) (adult albumin) and that for digitoxin was 4.12 x 10(6) (fetal albumin) and 2.7 x 10(6) (adult albumin). For salicylic acid, Ka was 38.4 x 10(3) (fetal albumin) and 35.8 x 10(3) (adult albumin) for the higher affinity site, and 2.7 x 10(3) (fetal albumin) and 4.3 x 10(3) (adult albumin) for the lower affinity site. This work shows that fetal and adult albumin have similar binding properties and corroborates our previous findings with furosemide.
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PMID:Binding of diazepam, salicylic acid and digitoxin to albumin isolated from fetal and adult serum. 181 15

Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.
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PMID:Binding of furosemide to albumin isolated from human fetal and adult serum. 187 50

Production of monoclonal antibodies against human chorionic gonadotropin (hCG) has been studied using hCG as an immunogen. Spleen cells of BALB/c mice immunized with hCG were fused with NS-1 mouse myeloma cells. This study reports the successful isolation of a hybrid clone secreting a monoclonal antibody specific for hCG. By using PEG 4,000 as a fusion agent, the fusion rates were between 42.0 and 50.2%. In total 842 hybridomas were produced. Among them, 403 hybridomas had hCG antibody production. After cloning twice by limiting dilution and alternately screening by enzyme immunoassay and by radioimmunoassay, there were 39 cell lines having specific antibody production. Among them, the No. 57-42-2 had the highest reactivity. By Ouchterlony test, the monoclonal antibody was shown to be IgG1. The affinity constant of the antibody to hCG was 0.6 x 10(9) 1/mole. In radioimmunoassay, the cross reactivity of the antibody to human luteinizing hormone (LH) and human follicle-stimulating hormone (FSH) was 1.5% and 0.7%, respectively. There was no cross reaction with human thyrotropin-stimulating hormone (TSH).
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PMID:Production of monoclonal antibodies to human chorionic gonadotropin. 324 19

The role of vitamin D in mineral uptake in the gastrointestinal tract (GIT) of mole-rats (Heterocephalus glaber and Cryptomys damarensis; family Bathyergidae), animals with a naturally impoverished vitamin D status, was investigated. We measured relative rates of passage of radioactive markers, mode of calcium (Ca) uptake, paracellular movement and the opening of voltage-sensitive Ca channels (VSCCs) along the GIT with and without oral vitamin D3 supplementation. The ratio of relative absorption of labelled 45Ca to [14C]polyethylene glycol ([14C]PEG) indicated that within 24 h more than 88% of the Ca in the diet had been absorbed. Most absorption occurred in the duodenum within 12 h. The contribution of the hindgut (caecum and proximal and distal colon) to total Ca absorption was small (approximately 11%). Only passive uptake occurred in the duodenum (serosal (S): mucosal (M) ratios approximately 1). Active uptake occurred in the hindgut (S:M > 2), although hindgut absorption appears to play a secondary role to passive uptake in the duodenum. Vitamin D3 supplementation had no effect on the mode of Ca uptake in either the small intestine or the hindgut. Although we found VSCCs in mole-rat intestinal epithelial cells, they occurred in very low concentrations. Calcium influx through VSCCs did not change following vitamin D stimulation. Furthermore, mole-rats pretreated with intraperitoneal (I.P.) 1,25(OH)2D3 showed no enhancement of VSCC Ca uptake, indicating that active uptake plays a minor role, if any, in GIT mineral absorption. Our data support the hypothesis that intestinal Ca transport in mole-rats is independent of both genomic and non-genomic vitamin D mediation.
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PMID:Intestinal calcium transport in mole-rats (Cryptomys damarensis and Heterocephalus glaber) is independent of both genomic and non-genomic vitamin D mediation. 757 99

General procedures are presented for the site-specific pegylation of peptides at the NH2-terminus, side-chain positions (Lys or Asp/Glu) or COOH-terminus using solid-phase Fmoc/tBu methodologies. A model tridecapeptide fragment of interleukin-2, IL-2(44-56)-NH2, was chosen for this study since it possesses several trifunctional amino acids which serve as potential sites for pegylation. The pegylation reagents were designed to contain either Nle or Orn, which served as diagnostic amino acids for confirming the presence of 1 PEG unit per mole of peptide. NH2-Terminal pegylation was carried out by coupling PEG-CH2CO-Nle-OH to the free NH2-terminus of the peptide-resin. Side-chain pegylation of Lys or Asp was achieved by one of two pathways. Direct side-chain pegylation was accomplished by coupling with Fmoc-Lys(PEG-CH2CO-Nle)-OH or Fmoc-Asp(Nle-NH-CH2CH2-PEG)-OH, followed by solid-phase assemblage of the pegylated peptide-resin and TFA cleavage. Alternatively, allylic protective groups were introduced via Fmoc-Lys(Alloc)-OH or Fmoc-Asp(O-Allyl)-OH, and selectively removed by palladium-catalyzed deprotection after assemblage of the peptide-resin. Solid-phase pegylation of the side-chain of Lys or Asp was then carried out in the final stage with PEG-CH2CO-Nle-OH or H-Nle-NH-(CH2)2-PEG, respectively. COOH-Terminal pegylation was achieved through the initial attachment of Fmoc-Orn(PEG-CH2CO)-OH to the solid support, followed by solid-phase peptide synthesis using the Fmoc/tBu strategy. The pegylated peptides were purified by dialysis and preparative HPLC and were fully characterized by analytical HPLC, amino acid analysis, 1H-NMR spectroscopy and laser desorption mass spectrometry.
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PMID:Pegylated peptides. II. Solid-phase synthesis of amino-, carboxy- and side-chain pegylated peptides. 820 Jul 30

The influence of poly(ethylene glycol)-lipid conjugates on phospholipid polymorphism has been examined using 31P-NMR and freeze--fracture electron microscopy. An equimolar mixture of dioleoylphosphatidylethanolamine (DOPE) and cholesterol adopts the hexagonal (HII) phase when hydrated under physiological conditions but can be stabilized in a bilayer conformation when a variety of PEG-lipid conjugates are included in the lipid mixture. These PEG conjugates produced an increase in the bilayer to hexagonal (HII) phase transition temperature and a broadening of the temperature range over which both phases coexisted. Further, the fraction of phospholipid adopting the bilayer phase increased with increasing mole fraction of PEG-lipid such that at 20 mole % DOPE--PEG2000 no HII phase phospholipid was observed up to a least 60 degrees C. Increasing the size of the PEG moiety from 2000 to 5000 Da (while maintaining the PEG--lipid molar ratio constant) increased the proportion of lipid in the bilayer phase. In contrast, varying the acyl chains of the PE anchor had no effect on polymorphic behavior. PEG--lipid conjugates in which ceramide provides the hydrophobic anchor also promoted bilayer formation in DOPE:cholesterol mixtures but at somewhat higher molar ratios compared to the corresponding PEG--PE species. The slightly greater effectiveness of the PE conjugates may result from the fact that these derivatives also possess a net negative charge. Phosphorus NMR spectroscopy indicated that a proportion of the phospholipid in DOPE:cholesterol:PEG--PE mixtures experienced isotropic motional averaging with this proportion being sensitive to both temperature and PEG molecular weight. Surprisingly, little if any isotropic signal was observed when PEG--ceramide was used in place of PEG--PE. Consistent with the 31P-NMR spectra, freeze-fracture electron microscopy showed the presence of small vesicles (diameter <200 nm) and lipidic particles in DOPE:cholesterol mixtures containing PEG--PE. We conclude that the effects of PEG--lipid conjugates on DOPE:cholesterol mixtures are 2-fold. First, the complementary "inverted cone" shape of the conjugate helps to accommodate the "cone-shaped" lipids, DOPE and cholesterol, in the bilayer phase. Second, the steric hindrance caused by the PEG group inhibits close apposition of bilayers, which is a prerequisite for the bilayer to HII phase transition.
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PMID:Poly(ethylene glycol)-lipid conjugates promote bilayer formation in mixtures of non-bilayer-forming lipids. 861 64

Large, unilamellar vesicles (LUV) composed of dipalmitoylphosphatidylcholine (DPPC) were made asymmetric in L-alpha-lysopalmitoylphosphatidylcholine (LPC) either by adding a small amount (total mole fraction = 0.003) of LPC to their outer leaflets (LUV-LPCout) or by extracting a small amount from outer leaflets which already contained 0.0015 mol fraction LPC (LUV-LPCin). The slow rate of the transbilayer redistribution of LPC allowed the asymmetric vesicles to be characterized with regard both to their physical properties and to their ability to fuse in the presence of poly(ethylene glycol) (PEG). The fraction of LPC extractable with bovine serum albumin was taken as a measure of LPC transbilayer asymmetry. The ratio of LPC available to that unavailable to BSA extraction was 6 for LUV-LPCout and 0.3 for LUV-LPCin. These asymmetries could not be enhanced significantly by increasing the vesicle LPC content. Measurements of the mixing and leakage of vesicle contents showed that LUV-LPCin fused in the presence of 15% (w/w) PEG without loss of contents but that LUV-LPCout did not fuse in the presence of up to 35% PEG. Vesicles prepared from palmitoyloleoylphosphatidylcholine could also be made asymmetric in LPC, but did not fuse even in the presence of 30% PEG. Quasi-elastic light scattering revealed that LUV-LPCin aggregated at 25 degrees C except when swollen by an osmotic gradient while LUV-LPCout were much less likely to aggregate. Trapped volume determinations suggested that neither type of vesicle was perfectly spherical in shape, but no correlation was found between fusogenicity and vesicle shape. Measurements of the fluorescence properties of TMA-DPH and of C6-NBD-PC suggested that the interface region of the outer leaflet of LUV-LPCin was slightly less ordered and less well packed than that of LUV-LPCout. This slight perturbation of the external vesicle surface correlated with the ability of juxtaposed vesicle bilayers to fuse.
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PMID:A slight asymmetry in the transbilayer distribution of lysophosphatidylcholine alters the surface properties and poly(ethylene glycol)-mediated fusion of dipalmitoylphosphatidylcholine large unilamellar vesicles. 882 98

Monolayers of dipalmitoyl-phosphatidylethanolamine (DPPE) mixing with various mole percentages of distearoyl-phosphatidylethanolamine (DSPE)-conjugated poly-(ethylene glycol) (PEG m.w. 750-5000) were deposited on DPPE-coated glass surfaces by the Langmuir-Blodgett method. Increasing percentages of grafted PEG in these supported lipid surfaces increasingly inhibit the adsorption of bovine serum albumin (BSA), laminin, and fibronectin. Increasing percentages of grafted PEG also inhibit the adhesion of erythrocytes, lymphocytes, and macrophages to these supported lipid surfaces. The adsorption of proteins on lipid coated glass surfaces were assayed by the fluorescence of FITC-labelled proteins. Cell adhesion was measured mainly by microscopic counting. The concentration of PEG-grafted lipids required for the inhibition of erythrocyte adhesion decreases with increasing molecular weight of the grafted PEG. The inhibitory effects are strongly dependent on the graft density of PEG at low concentrations, but weakly dependent on graft density at higher concentrations. For DSPE-PEG5000, the change of graft density dependency occurs approximately at the complete coverage of the lipid surface by the grafted polymer in the mushroom conformation (0.7 mol%), and the transition to partial brush conformation. The change-overs become less distinctive for grafted PEG of lower molecular weights, probably due to the failure of strictly mushroom and brush models of the polymer. The relative inhibitory efficiency is protein or cell dependent. The implication on the function of stealth liposomes is discussed.
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PMID:Grafted poly-(ethylene glycol) on lipid surfaces inhibits protein adsorption and cell adhesion. 921 54

Immunoliposomes composed of hydrogenated soy phosphatidylcholine, cholesterol, methoxypoly(ethylene glycol)-distearoyl phosphatidylethanolamine (mPEG-DSPE), and hydrazide-PEG-DSPE (mole ratio, 57:38:3.3:1.7) linked to periodate-oxidized chimerized mouse IgG (C225, anti-human epidermal growth factor receptor) were prepared by an optimized aggregation-free procedure. The antigen-binding activity of the immunoliposomes was well preserved. When injected intravenously into naive rats, the immunoliposomes (approximately 18 IgG per 100 nm liposome) exhibited long circulation times (MRT = 8.5 h, Cl = 0.2 ml/h). Subsequent injections of the immunoliposomes into the same animals resulted in rapid clearance (MRT < or = 0.7 h, Cl > or = 7 ml/h), which was accompanied by a significant increase in anti-C225 specific titers. Upon repeated injection or coinjection with the parent liposomes free C225 consistently exhibited prolonged circulation without any increase in C225-specific antisera, but was cleared quickly when administered into animals that had been pretreated with the immunoliposomes. Screening of the immunoliposome induced antisera against human polyclonal IgG and C225-derived Fab' fragment revealed that the immune response was specifically triggered by the constant human region of C225. These results demonstrate that the preparations of PEG-grafted immunoliposomes are more immunogenic than the free IgG component, which is of profound importance to the antibody-mediated liposomal drug delivery effort.
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PMID:Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted immunoliposomes. 927 Dec 60

We report x-ray scattering, rheological, and freeze-fracture and polarizing microscopy studies of a liquid crystalline hydrogel called Lalpha,g. The hydrogel, found in DMPC, pentanol, water, and PEG-DMPE mixtures, differs from traditional hydrogels, which require high MW polymer, are disordered, and gel only at polymer concentrations exceeding an "overlap" concentration. In contrast, the Lalpha,g uses very low-molecular-weight polymer-lipids (1212, 2689, and 5817 g/mole), shows lamellar order, and requires a lower PEG-DMPE concentration to gel as water concentration increases. Significantly, the Lalpha,g contains fluid membranes, unlike Lbeta' gels, which gel via chain ordering. A recent model of gelation in Lalpha phases predicts that polymer-lipids both promote and stabilize defects; these defects, resisting shear in all directions, then produce elasticity. We compare our observations to this model, with particular attention to the dependence of gelation on the PEG MW used. We also use x-ray lineshape analysis of scattering from samples spanning the fluid-gel transition to obtain the elasticity coefficients kappa and B; this analysis demonstrates that although B in particular depends strongly on PEG-DMPE concentration, gelation is uncorrelated to changes in membrane elasticity.
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PMID:The influence of polymer molecular weight in lamellar gels based on PEG-lipids. 964 87


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