Showing papers on "Serum albumin published in 1973"
TL;DR: The term ‘fusogenic’ is proposed to describe chemical, viral and physical agents that cause membranes to fuse and the possible biological significance of membrane fusion by fusogenic lipids is discussed.
Abstract: 1. The ability of a number of carboxylic acids, their esters, retinol and alpha-tocopherol to induce fusion of hen erythrocytes in vitro was investigated. 2. Some 30 different fat-soluble substances (100mug/ml) were found to cause the formation of multinucleated erythrocytes with a suspension of 3x10(8) erythrocytes/ml. The most effective agents induced fusion within 5-10min at 37 degrees C; some substances required about 1h. 3. Inclusion of Dextran 60C in the test medium minimized colloid osmotic lysis caused by exogenous lipids that induce cell fusion. 4. Cell swelling, followed by cell adhesion, was then seen to precede cell fusion. 5. Fusion occurred with C(10)-C(14) saturated carboxylic acids, with unsaturated, longer-chain carboxylic acids and their mono-esters; retinol, and to a lesser extent alpha-tocopherol, also caused cell fusion. 6. C(6)-C(9), C(15), C(16) and C(18) saturated carboxylic acids did not induce fusion within 4h; glyceryl dioleate was only weakly active, and glyceryl trioleate was inactive in the test system. 7. Fusion was facilitated by a high ratio of chemical agents to cell number and by incubation between pH5 and 6. It was inhibited by EDTA and by serum albumin. 8. Glyceryl mono-oleate caused both a similar fusion of several species of mammalian erythrocyte and the interspecific fusion of human and chicken erythrocytes. 9. The term ;fusogenic' is proposed to describe chemical, viral and physical agents that cause membranes to fuse. 10. The biochemical mechanisms involved and the possible biological significance of membrane fusion by fusogenic lipids are discussed.
247 citations
TL;DR: The findings suggest that binding of purified proteins for agarose substituted with 4-phenylbutylamine or with ϵ-aminocaproyl- d -tryptophan methyl ester results from the combined (and possibly mutually reinforcing) effects of hydrophobic and electrostatic forces.
185 citations
TL;DR: It is suggested that the observed activation of acetyl- CoA carboxylase by insulin may reflect changes in enzyme activity in the fat-cell resulting from the reduction of long-chain fatty-acyl-CoA that occurs in the presence of insulin.
Abstract: Rat epididymal fat-pads were incubated for 30min with glucose (2mg/ml) in the presence or absence of insulin. A twofold or greater increase in acetyl-CoA carboxylase activity was observed in extracts from insulin-treated tissue provided that assays were performed rapidly after extraction. This effect of insulin was evident whether or not extracts were prepared with albumin, and was not noticeably diminished by the presence of citrate or albumin or both in the assay. Incubation of extracts before assay led to activation of acetyl-CoA carboxylase and a marked diminution in the insulin effect. The enzyme in extracts was very sensitive to reversible inhibition by palmitoyl-CoA even in the presence of albumin (10mg/ml); inhibition persisted on dilution of enzyme and inhibitor. It is suggested that the observed activation of acetyl-CoA carboxylase by insulin may reflect changes in enzyme activity in the fat-cell resulting from the reduction of long-chain fatty-acyl-CoA that occurs in the presence of insulin. Activation of the enzyme with loss of the insulin effect on incubation of the extracts may be due to the slow dissociation of long-chain fatty acyl-CoA from the enzyme.
162 citations
TL;DR: The Hepa cell line synthesizes and secretes albumin at rates appreciably higher than previously reported hepatomas adapted to in vitro conditions and the significance of clonal variation is discussed in relation to the study of epigenetic control of albumin expression in somatic hybrid cells.
159 citations
TL;DR: It is confirmed that retinoic acid is not stored in any tissue and is transported in rat serum bound to serum albumin, and not by retinol-binding protein (the specific transport protein for plasma Retinol).
Abstract: The transport of retinoic acid in plasma was examined in vitamin A-deficient rats maintained on small doses of radioactively labelled retinoic acid. After ultracentrifugation of serum adjusted to density 1.21, most of the radioactivity (83%) was associated with the proteins of density greater than 1.21, and not with the serum lipoproteins. Gel filtration of the labelled serum on Sephadex G-200 showed that the radioactive label was associated with protein in the molecular-weight range of serum albumin. On polyacrylamide-gel electrophoresis almost all of the recovered radioactivity migrated with serum albumin. Similar esults were obtained with serum from a normal control rat given a single oral dose of [14C]retinoic acid. These findings indicate that retinoic acid is transported in rat serum bound to serum albumin, and not by retinol-binding protein (the specific transport protein for plasma retinol). Several tissues and the entire remaining carcase of each rat were extracted with ethanol–acetone to determine the tissue distribution of retinoic acid and some of its metabolites. The total recover of radioactive compounds in in the entire body of the rat was about 7–9μg, representing less than 5% or 10% respectively of the total administered label in the two dosage groups studied. The results confirm that retinoic acid is not stored in any tissue. Most of the radioactive material was found in the carcase, rather than in the specific tissues analysed. Two-thirds of the radioactivity in the carcase appeared to represent unchanged retinoic acid. Of the tissues examined, the liver, kidneys and intestine had relatively high concentrations of radioactive compounds, whereas the testes and fat-pads had the lowest concentrations.
152 citations
TL;DR: It has been shown that the ionized calcium concentration does not alter with prolonged venous stasis, and a more exact adjustment of 0·23 mg/100 ml of calcium for every 0·001 change in specific gravity is proposed.
Abstract: The relationship of plasma calcium levels to changes in plasma specific gravity, total protein, and albumin induced by venous stasis was investigated. Factors were derived for adjusting calcium results to offset the effects of variation in protein concentration and thus to make them of increased discriminatory value to the clinician. The validity of an existing specific gravity correction has been substantiated, but a more exact adjustment of 0.23 mg/100 ml of calcium for every 0.001 change in specific gravity is proposed. We recommend for automated laboratories that the factor based on albumin be used: 0.09 mg/100 ml of calcium should be subtracted from the total calcium value for every increase of 0.1 g in albumin above 4.6 g/100 ml, and a corresponding addition should be made for values of albumin below 4.6 g/100 ml.Using a calcium specific electrode, it has been shown that the ionized calcium concentration does not alter with prolonged venous stasis.
140 citations
TL;DR: It is suggested that an apoprotein-phospholipid complex is probably operative in the removal of membrane cholesterol and that in the absence of exogenous phospholipids, cellular lecithin may be utilized to form such a complex.
137 citations
TL;DR: The purpose of the present work was to determine whether changes in FFA concentration within this range would influence drug transport by plasma albumin, and to suggest that in the usual physiological concentrations, FFA binding is confined almost to long-chain FFA.
Abstract: Plasma albumin is the transport vehicle for many metabolites and drugs that are relatively insoluble in aqueous media. These substances are not linked covalently to albumin; they are bound physically, usually through a combination of nonpolar and electrostatic interactions. One of the most important metabolites transported by plasma albumin is free fatty acid (FFA) , the form in which fat is released from the adipose tissue storage depots.' The plasma FFA concentration is quite variable and is rapidly responsive to changes in nutritional status, physical activity, and environmental stimuli.2--' However, under ordinary conditions, the molar ratio of FFA to albumin in the plasma usually is in the range of 0.5 to 2.0, and it rarely exceeds 3.0.'~\" The purpose of the present work was to determine whether changes in FFA concentration within this range would influence drug transport by plasma albumin. The prevailing viewpoint is that physiological changes in the plasma FFA concentration have little or no influence on drug binding. This interpretation originated with Goodman's classical study of FFA binding to human plasma albumin.9 Goodman demonstrated that albumin contained three classes of binding sites for large organic anions. The association constants for FFA binding to the primary sites, ranging from 1.3 x lo-' M-1 for linoleate to 1.1 X lo8 M-l for oleate, were much larger than those reported for other organic ligands. Moreover, the presence of 1.8 pequiv of FFA did not influence the binding of methyl orange to albumin.!' The Scatchard model for methyl orange binding contained only two classes of sites, and the association constants were similar to those of the secondary and tertiary FFA binding sites. Based upon these observations, Goodman suggested that the second and third classes of albumin binding sites are shared by many organic ligands, whereas the primary sites, because of greater structural specificity, interact only with long-chain FFA. This general concept has been applied widely to drug transport; namely, that in the usual physiological concentrations. FFA binding is confined almost
136 citations
TL;DR: Transcapillary escape rate of albumin was found significantly increased in the long-term diabetics with microangiopathy, compared to the short-term diabetic and the non-diabetic groups, and it is assumed that the increased transcapillary Escape rate and the outflux ofalbumin reflect an increased microvascular permeability to albumin.
Abstract: Transcapillary escape rate of albumin (fraction of intravascular mass of albumin that passes to the extravascular space per unit time) was determined from the disappearance of intravenously injected 131I-human serum albumin during the first 60 min after injection in 14 non-diabetics, 12 short-term diabetics (mean duration of diabetes 2.6 years), and 21 long-term diabetics with microangiopathy (mean duration of diabetes 20 years). Transcapillary escape rate of albumin was found significantly increased in the long-term diabetics with microangiopathy, average 7.8 (S.D. 0.9) per cent/hour, compared to the short-term diabetic and the non-diabetic groups, average 5.5 (S.D. 1.0) and 5.9 (S.D. 1.0) per cent/hour, respectively. Similar results were obtained for the outflux of albumin (mass of intravascular albumin that passes to the extravascular space per unit time). It is assumed that the increased transcapillary escape rate and the outflux of albumin reflect an increased microvascular permeability to albumin, d...
115 citations
TL;DR: Rat liver polysomal RNA can direct the synthesis of albumin in a cell-free system derived from rabbit reticulocytes and can be enriched for albumin synthesizing activity by selective adsorption to nitrocellulose filters.
115 citations
TL;DR: It was concluded that serum albumin, sodium lactate and sodium pyruvate can be substituted for tissue fluid in the induction of capacitation of spermatozoa and fertilization of mouse eggs in vitro.
Abstract: Summary. The acrosome reaction of epididymal spermatozoa and fertilization in vitro of mouse eggs in chemically defined media without tissue fluid were investigated. About 8 to 10% of motile spermatozoa lost their acrosome but no eggs were penetrated when the spermatozoa and eggs were incubated in a basic medium (modified Krebs-Ringer bicarbonate solution containing glucose) for 5 to 7 hr. Addition of a single metabolic intermediate, such as sodium oxaloacetate or sodium pyruvate, to the basic medium increased the proportion of motile spermatozoa without an acrosome (19 to 34%) and the proportion of eggs penetrated (3\m=.\2 to 25\m=.\5%). Incubation of spermatozoa and eggs in the basic medium containing serum albumin of various species caused a further increase in the proportion of motile spermatozoa without an acrosome (50 to 65%) and in that of penetrated eggs (60\m=.\7 to 86%). The best medium for sperm capacitation and fertilization of mouse eggs in vitro, however, was the basic medium containing bovine serum albumin, sodium lactate and sodium pyruvate. The time required for sperm capacitation was 1 hr in this medium, and 2 hr in the medium containing only serum albumin. Certain components present in the oviducal fluid and in the cumulus egg clots, probably similar to serum albumin and sodium lactate or sodium pyruvate, appeared to be beneficial for the capacitation of spermatozoa and fertilization of eggs. It was concluded that serum albumin, sodium lactate and sodium pyruvate can be substituted for tissue fluid in the induction of capacitation of spermatozoa and fertilization of mouse eggs in vitro.
TL;DR: It is suggested that physiological changes in plasma non-esterified fatty acids levels can affect the availability of free tryptophan to the tissues by altering the binding properties of plasma albumin.
TL;DR: The production of interferon by human diploid cells stimulated by poly-I:C can be increased by pretreatment of the cells with interferons by combining priming with a superinduction schedule adapted from that described for rabbit kidney cultures.
Abstract: Summary
The production of interferon by human diploid cells stimulated by poly-I:C can be increased by pretreatment of the cells with interferon (priming effect). Large amounts of interferon (30000 units/ml) can be obtained by combining priming with a superinduction schedule adapted from that described for rabbit kidney cultures (Tan et al. 1970; Vilcek & Ng, 1971). Human plasma protein could replace bovine serum albumin in the production medium.
TL;DR: In the type of protein malnutrition found in Uganda this critical phase begins after serum-albumin concentration has fallen below 3·0 g per 100 ml.
TL;DR: Transcapillary escape rates of albumin and IgG were found significantly increased in the long-term diabetic group, and the TERIgG/TERalb ratio was nearly identical in the two groups, and very close to the ratio of the proteins' free diffusion coefficients.
Abstract: Transcapillary escape rates of albumin and IgG (fractions of intravascular mass of albumin and IgG that pass to the extravascular space per unit time) were determined simultaneously from the initial disappearance of intravenously injected 131I human albumin and 125I human IgG, in 10 long-term juvenile diabetics with microangiopathy (mean duration 20 years), and 9 non-diabetic subjects. Transcapillary escape rates of albumin (TERalb) and IgG (TERIgG) were found significantly increased in the long-term diabetic group, average 7.4 ± 1.1 (mean ± S.D.) and 4.4 ± 1.0 per cent/hour, respectively, compared to the non-diabetic group, mean 5.2 ± 1.0 and 3.0 ± 0.7 per cent/hour, respectively (p < 0.005). The TERIgG/TERalb ratio was nearly identical in the two groups, and very close to the ratio of the proteins' free diffusion coefficients. We assume that the present findings reflect an increased microvascular permeability to macromolecules, owing to an increased number or size of the large pores per unit sur...
TL;DR: Under the conditions chosen in these experiments there seems to exist only one binding site of the same type for all investigated benzodiazepines at the HSA molecule.
Abstract: The binding of eleven benzodiazepine derivatives to human serum albumin (HSA) was determined by means of sephadex gel filtration. The albumin binding of the substances was characterized by the percentage of bound drug, the binding constants k
+, K
1 and m, the number of binding sites per albumin molecule, and the free binding energy. Under the conditions chosen in these experiments there seems to exist only one binding site of the same type for all investigated benzodiazepines at the HSA molecule. The affinities of the benzodiazepines to this binding site are very different. It is discussed which part of the benzodiazepine molecule represents the main binding group.
TL;DR: Efforts were made to isolate fatty acid binding regions of the bovine albumin molecule after tryptic digestion of albumin which was bound to fatty acid-agarose, and some implications on the properties of the fatty acids-binding sites on albumin have been offered.
TL;DR: Scottish Blackface ewes were used to investigate the effect of protein deficiency during pregnancy on serum albumin, globulin, transferrin and plasma urea concentrations and the usefulness of the parameters as indices of the protein status of pregnant eWes was discussed.
Abstract: Scottish Blackface ewes were used to investigate the effect of protein deficiency during pregnancy on serum albumin, globulin, transferrin and plasma urea concentrations. Twenty-eight sheep were offered one of two iso-caloric diets in amounts which maintained energy intake at levels comparable to those found in hill sheep during winter. For half of the sheep (HP group) the crude-protein concentration was 11·8% and for the remainder (LP group) 6·0% in the dry matter. A further six sheep (group CL) were offered a diet containing 16·0% crude protein in amounts which prevented undernutrition. Concurrent changes in plasma volume and in certain serum proteins during pregnancy were determined in a second experiment.Serum globulins were not affected by protein intake and fell from 44·5 to 30·7 mg/ml during pregnancy. This was attributed mainly to a 30% increase in plasma volume which occurred during pregnancy.Serum albumin concentrations at the end of pregnancy were 29·3, 22·0 and 17'7 mg/ml and serum transferrin concentrations 400, 307 and 300 mg/100 ml in the CL, HP and LP groups respectively. Initial mean albumin and transferrin concentrations were 28·0 mg/ml and 383 mg/100 ml respectively. The usefulness of the parameters as indices of the protein status of pregnant ewes was discussed.Plasma urea N concentrations were related to the current protein intake of the animal. Mean values during late pregnancy were 26·0, 7'4 and 4·0 mg urea N/100 ml in the CL, HP, and LP) groups respectively. Limitations as to its usefulness were discussed.
TL;DR: The impact of phenylbutazone on warfarin metabolism is presented, particularly the alteration of its albumin binding, its pharmacokinetic behavior, and its hypoprothrombinemic effect.
Abstract: Modulation of the binding of drugs to plasma albumin is an important subject because of the serious clinical implications. The oral anticoagulant drugs are ideal agents for studying this phenomenon because their marked degree of binding to albumin produces significant displacement by other highly bound drugs. Furthermore, both the pharmacologic effect and the levels of oral anticoagulants in plasma can be quantitated readily. In addition to the intrinsic value of studying the albumin binding of oral anticoagulants, they also can provide an insight into the interaction of drugs with the receptor sites for pharmacologic activity. In this review, the number and strength of the binding sites on the albumin molecule for several oral anticoagulant drugs are considered. The albumin binding of warfarin precursors and metabolites is examined to further characterize the albumin binding sites for oral anticoagulants. The variation of the binding strength with changes in temperature, pH, and ionic strength of the supporting medium to evaluate the thermodynamic parameters of the interaction is recorded. The confirmation of these thermodynamic studies of the warfarin-albumin interaction by direct calorimetric measurement is reported. The impact of phenylbutazone on warfarin metabolism is presented, particularly the alteration of its albumin binding, its pharmacokinetic behavior, and its hypoprothrombinemic effect.
TL;DR: In this article, the levels of alpha-1 fetoprotein, IgG globulin, and albumin in 153 newborn infants were correlated with gestational age (length of pregnancy).
TL;DR: The approach described provides a means to separate leukocytes on the basis of what are likely to be preformed receptors to small endogenous hormones, and to study the physiologic importance and function of the receptors.
Abstract: Receptors for small endogenous hormones on human leukocytes were studied by insolubilizing the hormones and incubating them with the cells. Histamine, norepinephrine, and prostaglandin E2 (PGE2) were conjugated to either of two types of carrier: (bovine or rabbit) serum albumin or a random copolymer of DL-alanine and L-tyrosine. The conjugates were linked to agarose beads (Sepharose) and the resultant drug-conjugate-beads were incubated with leukocytes. Norepinephrine (when linked to its carrier via glutaraldehyde) and histamine preparations bound the majority of leukocytes. The binding appeared to be specific for the hormones tested. For example, the binding by histamine-rabbit serum albumin-Sepharose was prevented or reversed by high concentrations of histamine and histamine antagonists, but not by catecholamines or their pharmacologic antagonists. Similarly, binding of cells to the norepinephrine conjugate was inhibited by some catecholamines and propranolol, but not by histamine or histamine antagonists. Conjugates of norepinephrine linked via carbodiimide did not bind cells. The protein or copolymer carriers did not contribute to binding per se. The hormone-protein-conjugates bound more cells than the hormone-polymer conjugates. The former (unlike the free amines) failed to stimulate accumulation of cyclic AMP in leukocytes. The norepinephrine linked to polymer via glutaraldehyde, however, did stimulate leukocyte cyclic AMP accumulation, possibly because of the flexibility of the polymer. Columns of the various Sepharoses were used to determine the distribution of receptors to each hormone in mixed leukocyte populations. The majority of cells appeared to have receptors for both histamine and norepinephrine (bound through glutaraldehyde). Receptors to prostaglandins may have been detected by the column procedure, but their distribution could not be quantitated. The approach described provides a means to separate leukocytes on the basis of what are likely to be preformed receptors to small endogenous hormones, and to study the physiologic importance and function of the receptors.
TL;DR: In this paper, a yeast lactase, Maxilact, was immobilized in crosslinked polyacrylamide using a bead-polymerization technique, and the polymer beads obtained, containing the entrapped enzyme, were used for the preparation of lactose-free milk.
Abstract: A yeast lactase, Maxilact, was immobilized in crosslinked polyacrylamide using a bead-polymerization technique. The polymer beads obtained, containing the entrapped enzyme, were used for the preparation of lactose-free milk. The binding yield of the enzyme and residual enzymic activity in the “enzyme beads” were studied as a function of the amounts of monomeric acrylamide and cysteine and bovine serum albumin present as protecting agents in the monomer-enzyme solution prior to polymerization. A maximum of about 75% of the enzyme could be immobilized using a 20% (w/v) solution of acrylamide plus N, N′-methylenebis-acrylamide, whereas the highest activity quotient (bound to free) of about 60% was observed on using a 25% solution. The presence of cysteine increased the activity by up to 30% and that of serum albumin up to about 15%.
TL;DR: It is suggested that abnormal platelet aggregation in glomerular renal diseases may arise in part as a consequence of loss in the urine of plasma proteins normally responsible for inhibition of Platelet aggregation.
TL;DR: The number of cells capable of excluding trypan blue fell in a linear fashion over this period but oxygen consumption continued at a constant rate, and Supplementation with amino acids was found necessary to enhance the production of albumin.
TL;DR: The lipid A component of bacterial lipopolysaccharides (endotoxins), when complexed to bovine serum albumin (BSA) or human serumalbumin (HSA), was shown to be a potent pyrogen and rabbits could be protected against endotoxin fever by immunization with both lipid A and HSA.
Abstract: The lipid A component of bacterial lipopolysaccharides (endotoxins), when complexed to bovine serum albumin (BSA) or human serum albumin (HSA), was shown to be a potent pyrogen. Furthermore, rabbits could be protected against endotoxin fever by immunization with both lipid A·BSA and lipid A·HSA complexes. The results presented in this paper show that lipid A is responsible for the pyrogenic activity of endotoxins and their ability to induce pyrogenic immunity.
TL;DR: The results suggest that sulfonylureas bind reversibly to islet tissue but are normally restricted to the outside of the β-cells, which is more likely than not to stimulate insulin release by a direct action on theβ-cell plasma membrane.
Abstract: The study was aimed at testing the hypothesis that sulfonylureas do not readily penetrate the pancreaticβ-cells but more probably stimulate insulin release by a direct action on theβ-cell plasma membrane. Uptake of radioactively labelled tolbutamide and glibenclamide by microdissected pancreatic islets of obesehyperglycemic mice was compared with the uptake of 3-O-methyl-D-glucose, to which theβ-cells are permeable. In contrast to tolbutamide, glibenclamide was taken up in amounts exceeding the 3-O-methyl-D-glucose space of islets incubated in the absence of serum albumin. Uptake of the sulfonylureas was easily reversible. It was depressed by serum albumin, whereas glucose, leucine or diazoxide had no effects. Antimycin A,p-chloromercuriphenylsulfonic acid and chlorpromazine, all of which increase the uptake of extracellular space markers, strongly stimulated the islet uptake of tolbutamide and glibenclamide but had no effect on the uptake of glibenclamide by subcellular particles of homogenized islets. The results suggest that sulfonylureas bind reversibly to islet tissue but are normally restricted to the outside of theβ-cells.
TL;DR: The binding of l-tryptophan and drugs to the different fragments was studied by circular dichroism and equilibrium dialysis; only Fragments A and C were found to be active.
TL;DR: Results support the previous suggestion based on kinetic evidence that the albumin-like protein(s), in the anti-albumin precipitate from rat liver, is an albumin precursor.
Abstract: 1. A protein(s) of rat liver (precipitated from soluble extracts of the microsomal fraction by anti-albumin) yields albumin after limited hydrolysis by trypsin. 2. Evidence that the product of limited tryptic hydrolysis is albumin, is based upon ion-exchange chromatography, electrofocusing and peptide `mapping'. 3. The albumin `precursor' is recognized by anti-albumin and is apparently not distinguished from albumin by anti-albumin. 4. A small peptide is liberated from the presumptive albumin precursor during limited tryptic hydrolysis. This peptide is labelled by arginine, but not by leucine, lysine or methionine. 5. These results support our previous suggestion based on kinetic evidence that the albumin-like protein(s), in the anti-albumin precipitate from rat liver, is an albumin precursor.
TL;DR: In this paper, the effects of acyl-CoA derivatives (C8 to C20) on the activity of the yeast and Corynebacterium diphtheriae have been examined.