Showing papers on "Serum albumin published in 1982"
TL;DR: The adsorption of plasma FN onto both hydrophobic and hydrophilic surfaces from serum-containing solutions was found to depend on the serum concentration, suggesting the possibility that in long term cultures, cells deposit endogenous spreading factors on top of or in place of the adsorbed non-fibronectin serum proteins.
606 citations
TL;DR: The simplicity with which albumin has been coupled with DTPA by this method contrasts sharply with existing methods and is an attractive area of research for the labeling of a variety of proteins with a varietyof metallic radionuclides.
346 citations
TL;DR: The complete nucleotide sequence of human serum albumin mRNA has been determined from recombinant cDNA clones and from a primer-extended cDNA synthesis on the mRNA template, which verifies and refines the repeating homology in the triple-domain structure of the serumalbumin molecule.
Abstract: The complete nucleotide sequence of human serum albumin mRNA has been determined from recombinant cDNA clones and from a primer-extended cDNA synthesis on the mRNA template. The sequence is composed of 2078 nucleotides, starting upstream from a potential ribosome binding site in the 5' untranslated region. It contains all the translated codons and extends into the poly(A) at the 3' terminus. Part of the translated sequence codes for a hydrophobic prepeptide, Met-Lys-Trp-Val-Thr-Phe-Ile-Ser-Leu-Leu-Phe-Leu-Phe-Ser-Ser-Ala-Tyr-Ser, followed by a basic propeptide, Arg-Gly-Val-Phe-Arg-Arg. These signal peptides are absent from mature normal serum albumin and, so far, have not been identified in their nascent state in humans. A remaining 1755 nucleotides of the translated mRNA sequence code for 585 amino acids, which are in agreement, with few exceptions, with the published amino acid sequence for human serum albumin. The mRNA sequence verifies and refines the repeating homology in the triple-domain structure of the serum albumin molecule.
314 citations
TL;DR: In vivo results suggest that these conjugates formed with tri- and tetrapeptidic spacer arms are endocytosed by L1210 cells and that DNR is released intracellularly after digestion by lysosomal enzymes.
Abstract: Daunorubicin (DNR) has been conjugated to succinylated serum albumin by an amide bond joining the amino group of the drug and a carboxyl side chain of the protein either directly or with the intercalation of a peptide spacer arm varying from one to four amino acids. During in vitro incubation with lysosomal hydrolases, intact DNR could be released extensively only from conjugates prepared with a tri- or tetrapeptide spacer arm. These latter conjugates remained very stable in the presence of serum. When tested in vivo against the intraperitoneal form of L1210 leukemia, the conjugates in which DNR was linked to serum albumin directly or via one amino acid were completely inactive but the conjugate with a dipeptide spacer arm was not more active than free DNR. In parallel with the in vitro studies, the best therapeutic results were obtained with the conjugates formed with tri- and tetrapeptidic spacer arms; they were much more active than DNR, inducing a high percentage of long-term survivors. Thus, use of a tri- or tetrapeptide spacer arm is essential to obtain DNR-protein conjugates that remain stable in serum and from which DNR can be released through the action of lysosomal hydrolases. The in vivo results suggest, moreover, that these conjugates are endocytosed by L1210 cells and that DNR is released intracellularly after digestion by lysosomal enzymes. This conjugation method can be applied to other drugs possessing a free amino group and to various potential carriers, such as antibodies, polypeptide hormones, and glycoproteins, that have amino or carboxyl side chains.
301 citations
Journal Article•
TL;DR: In this paper, the authors performed nutritional assessment on 47 patients admitted to a nephrology service; renal failure was present in 39 of the 47 patients, and low serum albumin values were also found in 11 of the 15 patients with infection.
139 citations
TL;DR: Alterations in the liver microcirculation were characterized by use of the multiple-indicator dilution technique in 25 cirrhotic patients undergoing hemodynamic evaluation of portal hypertension and model analysis of the unimodal data indicated that the spectrum of findings could best be explained by progressive development of a barrier to exchange by progressive capillarization of the microvascular bed.
Abstract: Alterations in the liver microcirculation were characterized by use of the multiple-indicator dilution technique in 25 cirrhotic patients undergoing hemodynamic evaluation of portal hypertension. Hepatic vein outflow dilution curves were obtained after portal vein or hepatic artery injections of a vascular reference substance (labeled erythrocytes) and of diffusible substances (labeled albumin and sucrose). In 23 of these patients (19 with alcoholic cirrhosis and 4 with postnecrotic cirrhosis), unimodal erythrocytes and albumin curves were obtained; the immediately accessible albumin space ranged from normal values (that were substantially larger than the erythrocyte space) to low values (that were little larger than the erythrocyte space). In parallel with this, the hepatic extraction of indocyanine green decreased and was correlated with the albumin space (r = 0.821, P less than 0.001). The form of labeled sucrose curves showed progressive changes indicating limited diffusion into the interstitial space. In contrast, bimodal curves were found in two patients (with macronodular cirrhosis); a large proportion of all labels appeared simultaneously in the early part of the outflow curves. Model analysis of the unimodal data indicated that the spectrum of findings could best be explained by progressive development of a barrier to exchange by progressive capillarization of the microvascular bed, and the form of the bimodal data suggested that large vessel shunting was occurring. Both changes, in turn, will contribute to the reduced extraction of protein-bound materials in cirrhosis.
137 citations
TL;DR: It is suggested that cysteine-34 does not participate in disulfide bonding because the NH2 terminus of proalbumin remains loosely bound to the membrane, attached by a hydrophobic segment of the chain at residues 21-27.
121 citations
TL;DR: The stimulatory effect of histamine on the transcapillary transport could not be inhibited by a histamine H1− receptor antagonist, mepyramine and metiamide prevented both ultrastructural changes and albumin penetration in the brain capillaries to occur.
Abstract: The effect of histamine administered via the common carotid artery on the transport processes of brain capillaries was investigated in rats. The fine structure of endothelial cells and the glial end-feet system was studied by electron microscopy and the serum albumin was visualized for light microscopy by the peroxidase-antiperoxidase (PAP) immunohisto-chemical reaction. Sixty microgram per milliliter histamine enhanced the penetration of serum albumin into the capillaries while the number of pinocytotic and coated vesicles significantly increased in the capillary endothelium. Oedematous swelling of the glial end-feet system was also observed. The stimulatory effect of histamine on the transcapillary transport could not be inhibited by a histamine H1-receptor antagonist, mepyramine. By contrast, metiamide, a histamine H2-receptor antagonist prevented both ultrastructural changes and albumin penetration in the brain capillaries to occur.
111 citations
TL;DR: It is proposed that the formation of covalent steroid-protein adducts is a generalized phenomenon which may contribute to the pathological effects produced by elevated levels of certain endogenous steroids.
Abstract: The incubation of albumin with cortisol or 16 alpha-hydroxyestrone results in the formation of covalent steroid-protein adducts. The rate of adduct formation increases in the presence of sodium cyanoborohydride (NaCNBH3), indicating that the reaction proceeds nonenzymatically through a Schiff base intermediate. Under nonreducing conditions, a stable adduct forms with cortisol and 16 alpha-hydroxyestrone but not with estrone, which lacks a hydroxyl group adjacent to the reactive carbonyl. It is hypothesized that a Heyns rearrangement involving the adjacent hydroxyl group traps the Schiff base and produces a stable ketoamine adduct. The binding of 16 alpha-hydroxyestrone and cortisol to albumin is significantly inhibited by acetylsalicylic acid, which has been shown to acetylate an epsilon-amino group of a lysine residue in albumin. High-pressure liquid chromatography analysis of an acid hydrolysate of 16 alpha-hydroxyestrone-albumin shows that a product containing 16 alpha-hydroxyestrone coelutes with a standard prepared by reacting 16 alpha-hydroxyestrone with the epsilon-amino group of lysine. We propose that the formation of covalent steroid-protein adducts is a generalized phenomenon which may contribute to the pathological effects produced by elevated levels of certain endogenous steroids.
100 citations
TL;DR: For those drugs, binding to α1-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers, and for each of these drugs there was a strong correlation between the serumα1-glycoprotein concentration and the percentage binding.
Abstract: The binding of 8 β-adrenergic blocking drugs to human serum albumin, to α1-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to α1-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum α1-glycoprotein concentration and the percentage binding.
95 citations
Journal Article•
TL;DR: Twenty-two of 27 human benign hyperplastic prostate cytosol samples were found to contain protein immunochemically similar to estramustine-binding protein (EMBP) purified from rat ventral prostate as determined by the EMBP radioimmunoassay method.
Abstract: The [3H]estramustine-binding macromolecule in human prostate was partially characterized using a number of chromatographic procedures. Although human estramustine-binding protein (HEMBP) had a marked tendency to aggregate in several systems, a molecular weight of about 54,000 was determined by gel filtration on Sephacryl S-200 Superfine and high-performance liquid chromatography. A sedimentation-coefficient of about 3.6S was obtained for HEMBP when analyzed by sucrose density gradient centrifugation. Isoelectric focusing in polyacrylamide gels indicated an isoelectric point of 4.7 to 4.8, which was in agreement with the elution position of HEMBP following chromatofocusing on Polybuffer Exchanger 94. Furthermore, HEMBP was eluted from diethylaminoethyl-Sepharose with 0.23 M KCl, was retained by concanavalin A-Sepharose (indicating that HEMBP is a glycoprotein), but did not interact with Affi-Gel Blue. Special efforts were concentrated on establishing that HEMBP was a species distinct from human serum albumin. Separation between the [3H]estramustine-labeled HEMBP and the [3H]estramustine-human serum albumin complex was obtained both on sucrose density gradients by chromatography on Affi-Gel Blue, by chromatofocusing, by gel filtration, by isoelectric focusing, and on concanavalin A-Sepharose by affinity chromatography. Twenty-two of 27 human benign hyperplastic prostate cytosol samples were found to contain protein immunochemically similar to estramustine-binding protein (EMBP) purified from rat ventral prostate as determined by the EMBP radioimmunoassay method. Concentrations from 0.2 to 139.6 ng EMBP per mg of total cytosolic protein (mean, 19.3) were determined. Furthermore, four of seven prostatic cancer specimens as well as two of two normal prostatic specimens were also found to contain rat EMBP-immunoreactive material. The unequivocal demonstration of the presence of a HEMBP is of great potential interest in consideration of estramustine phosphate (Estracyt) therapy against prostatic carcinoma. It is not inconceivable that the concentration of HEMBP in the carcinomatous tissue will be of significance in determining the drug uptake in the malignant tissue.
TL;DR: Two serum‐free chemically defined media are developed that support the growth in culture of human diploid fibroblasts to the same extent as Eagle's basal medium supplemented with 10% fetal bovine serum (FBS).
Abstract: We have developed two serum-free chemically defined media (RITC 78-6 and RITC 80-7) that support the growth in culture of human diploid fibroblasts to the same extent as Eagle's basal medium (BME) supplemented with 10% fetal bovine serum (FBS). These two media contain modified Eagle's minimum essential medium (MEM) supplemented with nonessential amino acids, various trace metals, organic compounds and growth factors [insulin, mouse epidermal growth factor (m-EGF), transferrin and triiodothyronine (T3)]. RITC 80-7 medium differs from RITC 78-6 in that it contains thymidine, hypoxanthine, and vitamin B12 and supports the long-term serial cultivation of human diploid cultures. The addition of commercial bovine serum albumin (BSA, 5 g/liter) to the medium enhances cell growth. This effect is not observed if BSA is first delipidized, but reconstitution of BSA with certain lipids restores its ability to promote growth. BSA has an inhibitory effect on cellular attachment but this is overcome when fibronectin (FN, 10 mg/liter is added to the medium.
TL;DR: The biosynthetic mechanism of prostaglandin D2 in human platelet-rich plasma has been investigated and formation was observed in association with thrombin-evoked platelet aggregation in this system and was proportional to the number of platelets and the concentration of serum albumin.
TL;DR: Since the method is rapid, extremely sensitive, and specific, it appears to be the best method currently available for the measurement of serum primary bile acids.
Journal Article•
TL;DR: Results show that fatty acids are bound to a number of membrane-associated proteins, both glycosylated and unglycosylation, via linkages that resist purification of the proteins on SDS-polyacrylamide gel electrophoresis and are suggestive of covalent attachment of fatty acids to these proteins.
TL;DR: It is concluded that charge is an important determinant of protein entry into the CSF.
Abstract: Entry of proteins into the cerebrospinal (CSF) from the blood is partially determined by the size of the protein. To determine whether other characteristics of proteins influence CSF entry, proteins or protein fragments were iodinated, inoculated intravenously, and serum and CSF were sampled at later times. The Fc fragment of immunoglobulin G (IgG) did not enter the CSF significantly better than the Fab fragment suggesting that choroidal Fc receptors are not of importance for selective immunoglobulin entry. To determine the role of protein charge on entry, bovine serum albumin [isoelectric point (pI) = 3.9] was chemically altered to provide an albumin with an average pI of 6 (A-6) and another with a pI of 8.5 (A-8). All albumins were of the same size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A-8 entered the CSF approximately 10-fold better than the native albumin. A-6 was intermediate, entering approximately twofold better. At the time of increased CSF protein concentration during an acute viral encephalitis these differences were narrowed but not eliminated. It is concluded that charge is an important determinant of protein entry into the CSF.
TL;DR: In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady‐state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken, suggesting that serum salicylate also altered VPA metabolism.
Abstract: In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.
TL;DR: Both the total and free serum concentrations of phenytoin and phenobarbitone were decreased in late pregnancy, and the reduction correlated positively with the gestational age and negatively with the serum albumin concentration.
Abstract: 1 The effect of pregnancy on the binding of phenytoin and phenobarbitone to serum proteins was studied in normal women and in drug treated epileptic women. 2 The binding of both drugs was reduced during pregnancy. The reduction correlated positively with the gestational age and negatively with the serum albumin concentration. 3 In spite of the increase in unbound fraction, both the total and free serum concentrations of phenytoin were decreased in late pregnancy.
TL;DR: The inhibition of proline uptake by oleic acid was overcome by the addition of serum albumin and the data presented indicate that the previously reported stimulation of prolines uptake by albumin could be related to its fatty acid binding properties.
Abstract: The Na+-dependent synaptosomal uptakes of proline, aspartic acid, glutamic acid, and gamma-aminobutyric acid were strong inhibited by monounsaturated fatty acids. With oleic acid, half-maximal inhibition was observed at about 15 microM. The Na+-independent uptakes of leucine, phenylalanine, histidine, and valine were less sensitive to inhibition by the unsaturated fatty acids. In contrast, the uptakes of all of these amino acids were unaffected by saturated fatty acids. The inhibition of proline uptake (and that of the other Na+-dependent amino acids) by oleic acid was overcome by the addition of serum albumin and the data presented further indicate that the previously reported stimulation of proline uptake by albumin could be related to its fatty acid binding properties.
TL;DR: The results show that the addition of fat reduced glucose and hepatic related metabolic complications and avoided adverse side effects of hypoglycemia, hyperosmolar coma, and hypertriglyceridemia.
Abstract: The limitations of glucose-based TPN solutions are high glucose concentration, high osmolality, lack of fat, and essential fatty acids, which result in glucose intolerance and hepatotoxic effects. We replaced one-third of the calories in a standard amino acid-glucose solution with Liposyn 10% for 14 days in 23 critically ill men who needed total parenteral nutrition. Serial measurements included weight, albumin, glucose, triglyceride concentrations, and liver function tests. Serum osmolality was calculated, and found to remain constant. Body weight and serum albumin were maintained. Minor changes occurred in hepatic enzymes which were physiologically insignificant. Glycosuria occurred in 15%. Adverse side effects of hypoglycemia, hyperosmolar coma, and hypertriglyceridemia were avoided. Our results show that the addition of fat reduced glucose and hepatic related metabolic complications.
TL;DR: Hemin was conjugated to aminoethyl-agarose with high efficiency using 1,1′-carbonyldiimidazole as a condensing agent and was an efficient affinity resin for certain heme-binding proteins, whereas hemoglobin did not bind to the resin.
TL;DR: It is suggested that these glycoproteins, synthesized by the liver in response to an inflammatory stimulus, may act as ‘non-specific blocking factors’ protecting tumors against the host's immunological attack, and contribute to the ‘immune escape’ of the tumor.
Abstract: Acute-phase reactant proteins reach abnormally high levels in patients with cancer, and correlate with the extent of disease. In this study, several acute-phase glycoproteins, and serum albumin as a control, were tested at different concentrations for their ability to modify the blastogenic response of lymphocytes from 30 normal donors to PHA and the chemotactic response of monocytes from 15 normal donors to casein. In high concentrations approximating those found in cancer patients, but not in normal concentrations, haptoglobin and fibrinogen inhibited both functions to different degrees. Orosomucoid inhibited only monocyte chemotaxis, while ceruloplasmin and α1-antitrypsin affected neither function.
TL;DR: Observations resolve a discrepancy existing in the literature concerning the sedimentation rate of human P components in density gradient ultracentrifugation and shed new light on its behaviour with respect to Ca2+ which may be relevant to the deposition of P component in amyloidosis.
TL;DR: It is suggested that monensin arrests the intracellular transport of proalbumin before the site where its conversion takes place, and this inhibition of secretion by monens in primary cultured rat hepatocytes was accompanied by an intrACEllular accumulation of pro albumin.
TL;DR: Uterine fluid cholesterol affinity, therefore, correlated with sperm capacitation activity in utero, and Serum albumin has been identified as a uterine sterol acceptor.
Abstract: Cholesterol from rabbit sperm cells was bound by uterine fluid proteins following intrauterine insemination into ovulating does. Serum albumin has been identified as a uterine sterol acceptor. Progesterone administration suppressed binding and elevated the concentration of cholesterol, phospholipid, and protein. Uterine fluid cholesterol affinity, therefore, correlated with sperm capacitation activity in utero.
TL;DR: The results indicated that glucose reacted with albumin by a nonenzymatic process involving Schiff base formation and Amadori rearrangement to a stable ketoamine derivative.
TL;DR: It is demonstrated that estrogen suppression of glucocorticoid regulated secreted proteins also occurs in isolated pieces of liver tissue and that suppression requires all three of the tested hormones.
TL;DR: The rates of disappearance from the serum of isotopically labeled albumin and P‐IgA were observed to increase dramatically during lactation, suggesting that both of these two milk proteins might be derived at least in part from the semen of lactating mice.
Abstract: The metabolism of albumin and IgA was studied in normal and lactationg mice. Lactation resulted in significant changes in the metabolism of these proteins. The serum albumin concentration was lowered from 47 mg/ml in normals to 24 mg/ml in lactating mice. However, only a slight decrease in the serum concentration of IgA was observed during lactation. The proportion of polymeric and monomeric IgA in serum and milk was evaluated by gel exclusion chromatography. The onset of lactatin led to a rise in the proportion of polymeric IgA (P-IgA) in serum from 37% to 51%. The proportion of P-IgA in milk was 65% and remained constant throughout lactation. P-IgA and albumin were shown to be efficiently transferred from the serum of lactating mice into their milk. Serum decay studies were performed to evaluate the turnover of the serum pools during lactation. The rates of disappearance from the serum of isotopically labeled albumin and P-IgA were observed to increase dramatically during lactation, suggesting that both of these two mild proteins might be derived at least in part from the serum. The sites of synthesis of mild IgA (local vs. extra-mammary gland) were evaluated by determining the extent of dilution of isotopically labeled serum IgA during transport through the mammary gland into the milk. Early in lactation, the majority of the IgA in mouse milk appeared to be derived from distant sites and transferred via the blood to the mammary gland. However, by day 8 of lactation, the isotopically labeled P-IgA in milk was significantly diluted by the IgA synthesized in the mammary gland. Albumin and IgG were not diluted by local synthesis indicating that these proteins were exclusively serum-derived.