Showing papers on "Serum albumin published in 1986"

Assessment of the Free Fraction of 25-Hydroxyvitamin D in Serum and Its Regulation by Albumin and the Vitamin D-Binding Protein

Abstract: We measured the free fraction of 25-hydroxyvitamin D (25OHD) in human serum and determined that 25OHD bound to a component with an affinity constant of 7 × 108 M-1 and a concentrationof 4.5 × 10-6 M. This concentration was equal to that of the vitamin D-binding protein (DBP) in the same serum sample. We removed DBP from the serum using actin affinity columns and found that the affinity for 25OHD of the remaining serum components was equivalent to that of human serum albumin (6 × 105 M-1). We then measured the free fractions of 25OHD, DBP, and albumin in normal and cirrhotic subjects. Wecalculated that 88 ± 3% (±SD) and 83 ± 8% of the 25OHD were bound to DBP in the serum of normal and cirrhotic subjects, respectively. We compared previously reported data for the free fraction and the free concentration of 1,25-dihydroxyvitamin Din these subjects with the current data for the free fraction and free concentrationof 25OHD. Thetotal concentrations and free fractions of both metabolites correlated to each other...

Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis.

Abstract: The interaction of homologous and heterologous albumin-gold complex (Alb-Au) with capillary endothelium was investigated in the mouse lung, heart, and diaphragm. Perfusion of the tracer in situ for from 3 to 35 min was followed by washing with phosphate-buffered saline, fixation by perfusion, and processing for electron microscopy. From the earliest time examined, one and sometimes two rows of densely packed particles bound to some restricted plasma membrane microdomains that appeared as uncoated pits, and to plasmalemmal vesicles open on the luminal front. Morphometric analysis, using various albumin-gold concentrations, showed that the binding is saturable at a very low concentration of the ligand and short exposure. After 5 min, tracer-carrying vesicles appeared on the abluminal front, discharging their content into the subendothelial space. As a function of tracer concentration 1-10% of plasmalemmal vesicles contained Alb-Au particles in fluid phase; from 5 min on, multivesicular bodies were labeled by the tracer. Plasma membrane, coated pits, and coated vesicles were not significantly marked at any time interval. Heparin or high ionic strength did not displace the bound Alb-Au from vesicle membrane. No binding was obtained when Alb-Au was competed in situ with albumin or was injected in vivo. Gold complexes with fibrinogen, fibronectin, glucose oxidase, or polyethyleneglycol did not give a labeling comparable to that of albumin. These results suggest that on the capillary endothelia examined, the Alb-Au is adsorbed on specific binding sites restricted to uncoated pits and plasmalemmal vesicles. The tracer is transported in transcytotic vesicles across endothelium by receptor-mediated transcytosis, and to a lesser extent is taken up by pinocytotic vesicles. The existence of albumin receptors on these continuous capillary endothelia may provide a specific mechanism for the transport of albumin and other molecules carried by this protein.

Induction of the acrosome reaction in human spermatozoa by a fraction of human follicular fluid

Abstract: Human ejaculated spermatozoa were washed through a Percoll gradient, preincubated for 10 hr in a defined medium containing serum albumin, and then induced to undergo rapid acrosome reactions by addition of human follicular fluid or a Sephadex G-75 column fraction of the fluid. Induction by follicular fluid did not occur when the spermatozoa were preincubated for only 0 or 5 hr. The reactions were detected by indirect immunofluorescence using a monoclonal antibody directed against the human sperm acrosomal region. The percentage of acrosomal loss counted by transmission electron microscopy agreed with that counted by immunofluorescence. The apparent molecular weight of the Sephadex G-75 fraction containing the peak of acrosome reaction-inducing activity was 45,000 ± 4,200 (SD). The occurrence of physiological acrosome reactions was supported by: assessing motility (no significant loss of motility occurred during the treatment period when sperm were preincubated with bovine serum albumin), transmission electron microscopy (the ultrastructural criteria for the acrosome reaction were met), and zona-free hamster oocyte binding and penetration (spermatozoa pretreated with the active fraction of follicular fluid, then washed and incubated with oocytes, showed significantly greater binding to and penetration of oocytes). The stimulation of the acrosome reaction by follicular fluid is apparently not due to blood serum contamination; treatment of preincubated spermatozoa with sera from the follicular fluid donors had no effect on the spermatozoa. The nature of the active component(s) in that fraction is currently being investigated.

Site-specific modification of albumin by free radicals. Reaction with copper(II) and ascorbate.

Abstract: Exposure of albumin to Cu(II) (10-100 microM) and ascorbate (0.1-2 mM) results in extensive molecular modifications, indicated by decreased fluorescence and chain breaks. The rate of utilization of molecular oxygen and ascorbate as a function of Cu(II) concentration is non-linear at copper/albumin ratios of greater than 1. It appears that Cu(II) bound to the tightest albumin-binding site is less available to the ascorbate than the more loosely bound cation. SDS/polyacrylamide-gel electrophoresis reveals new protein bands corresponding to 50, 47, 22, 18 and 3 kDa. For such a cleavage pattern, relatively few (approximately 3) and rather specific chain breaks occurred. Repeated addition of portions of ascorbate to the albumin/Cu(II) mixture results in increased intensity of the new bands. The absence of Cu(II) or the presence of metal chelating agents is inhibitory. There was no evidence of intermolecular cross-linking or of the formation of insoluble, albumin-derived, material. A mechanism is proposed wherein the loosely bound Cu(II) participates in a Fenton-type reaction. This generates OH. radicals, which rapidly inter-react with the protein and modify it in a 'site-specific' manner.

Changes in sperm plasma membrane lipid diffusibility after hyperactivation during in vitro capacitation in the mouse.

Abstract: We have used the technique of fluorescence recovery after photobleaching to measure the diffusibility of the fluorescent lipid analogue, 1,1'-dihexadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate on the morphologically distinct regions of the plasma membranes of mouse spermatozoa, and the changes in lipid diffusibility that result from in vitro hyperactivation and capacitation with bovine serum albumin. We found that, as previously observed on ram spermatozoa, lipid analogue diffusibility is regionalized on mouse spermatozoa, being fastest on the flagellum. The bovine serum albumin induced changes in diffusibility that occur with hyperactivation are also regionalized. Specifically, if we compare serum incubated in control medium, which maintains normal motility, with those hyperactivated in capacitating medium, we observe with hyperactivation an increase in lipid analogue diffusion rate in the anterior region of the head, the midpiece, and tail, and a decrease in diffusing fraction in the anterior region of the head.

Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration.

Abstract: During liver regeneration induced by CCl4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [3H]thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and pro alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl4 administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl4-induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process.

Structure and lipid binding properties of serum albumin.

Abstract: Publisher Summary Bovine albumin is composed of a single polypeptide chain containing 581 amino acid residues, and there are many regions of homology in the amino acid sequence, and the polypeptide chain is folded into three similar globular domains, designated I, II, and III, composed of 185, 192, and 204 amino acid residues, respectively. This chapter describes the structure and lipid binding properties of serum albumin. The primary and secondary fatty acid binding sites are located between or within loops lined with hydrophobic amino acid side chains. Two methods have been employed to localize the binding sites within the albumin structure; one is fluorescence spectroscopy, and the other is proteolytic cleavage followed by equilibrium binding to the resulting protein fragments. Both methods of analysis indicate that the strongest fatty acid binding site is located within the third domain. The chapter indicates that fatty acid binding is associated with small conformational changes that allow the fatty acid to penetrate into the interior of the globular protein structure and enable the albumin binding sites to adapt to the configuration of the fatty acyl chain.

Aflatoxin B1 binding to plasma albumin and liver DNA upon chronic administration to rats.

Abstract: The hepatocarcinogen aflatoxin B1 (AFB1) was administered to male Wistar rats by oral intubation in either single or repeated doses and the binding to plasma protein and liver DNA determined. Twenty-four hours after a single dose (3.5-200 micrograms/kg AFB1) a constant ratio was found between levels of aflatoxin bound to plasma protein and that bound to liver DNA. In total 0.98-2.15% of the administered dose was bound to the plasma protein at this time point. In the chronic study rats received two doses of 0.5 microgram AFB1/day and groups of animals were killed on days 2, 3, 7, 14, 21 and 24. Binding of aflatoxin to plasma protein accumulated to a level 3-fold higher than that seen after a single dose. Levels of binding reached a plateau between days 7 and 14 of treatment and then remained stable until the end of the experiment. Binding to DNA also accumulated, 2.5-fold and in parallel to plasma protein, binding reached a plateau between days 7 and 14 of treatment. In both the chronic and acute studies fractionation of the plasma proteins by Sephadex G-200 chromatography showed that all detectable bound aflatoxin was associated with a single peak corresponding to albumin. Thus, a constant ratio was observed, after chronic or single exposure, between the concentration of plasma albumin-bound aflatoxin and that bound to DNA of the liver, the target organ for carcinogenesis by AFB1. In order to investigate the proposed role of AFB1 in the aetiology of primary hepatocellular carcinoma in man it would be of great value to have a method for assessing long-term human exposure at an individual level. The relevance of the observations presented in this paper are discussed in the light of such a requirement.

The selective suppression of immunogenicity by hyaluronic acid.

Abstract: A hyaluronidase-sensitive component of human peritoneal fluid from a patient with Wilms' tumor when injected into rabbits has been shown to suppress the formation of humoral precipitating antibodies to certain major classes of proteins present in the fluid Furthermore, it has been found that hyaluronic acid, when included with certain test antigens (serum albumin, fetuin) or antigen mixtures (tumor isolates or mixtures of albumin, immunoglobulin G and immunoglobulin M), produces a marked distortion or complete blockage of immunoelectrophoresis precipitin arcs, as well as altered gel chromatography elution profiles These findings that hyaluronic acid can interfere profoundly with both the elicitation of a complete antibody response and the formation of "normal" patterns of antigen-antibody precipitates in laboratory tests supports the possibility that this polysaccharide may play an immuno-regulatory role by masking potential immunogens Consideration of the mechanisms for these in vivo and in vitro effects suggests that there may be some common basis in an "excluded volume" property of the hyaluronate, but this does not appear sufficient to explain the complexity and selectivity of the observed phenomena

Transfer of oleic acid between albumin and phospholipid vesicles

Abstract: The net transfer of oleic acid between egg phosphatidylcholine unilamellar vesicles and bovine serum albumin has been monitored by 13C NMR spectroscopy and 90% isotopically substituted [1-13C]oleic acid. The carboxyl chemical shifts of oleic acid bound to albumin were different from those for oleic acid in phospholipid vesicles. Therefore, in mixtures of donor particles (vesicles or albumin with oleic acid) and acceptor particles (fatty acid-free albumin or vesicles), the equilibrium distribution of oleic acid was determined from chemical shift and peak intensity data without separation of donor and acceptor particles. In a system containing equal masses of albumin and phospholipid and a stoichiometry of 4-5 mol of oleic acid per mol of albumin, the oleic acid distribution was pH dependent, with greater than or equal to 80% of the oleic acid associated with albumin at pH 7.4; association was greater than or equal to 90% at pH 8.0. Decreasing the pH below 7.4 markedly decreased the proportion of fatty acid bound to albumin; at pH 5.4, less than or equal to 10% of the oleic acid was bound to albumin and greater than 90% was associated with vesicles. The distribution was reversible with pH and was independent of whether vesicles or albumin acted as a donor. These data suggest that pH may strongly influence the partitioning of fatty acid between cellular membranes and albumin. The 13C NMR method is also advantageous because it provides information about the structural environments of oleic acid bound to albumin or phospholipid, the ionization state of oleic acid in each environment, and the structural integrity of the vesicles. In addition, minimum and maximum limits for the exchange rates of oleic acid among different environments were obtained from the NMR data.

Effects of fetal calf serum and bovine serum albumin on in vitro maturation and fertilization of bovine and hamster cumulus-oocyte complexes.

Abstract: Bovine serum albumin (BSA) and fetal calf serum (FCS) were evaluated as protein supplements for in vitro maturation and fertilization of oocytes from cows and hamsters. BSA and low doses of FCS (0.1 or 1.0%) did not support viability or maturation of the cumulus-oocyte complex as well as higher doses of FCS (5, 10, or 20%) for either species. BSA failed to support cumulus expansion for bovine or hamster cumulus-oocyte complexes. All doses of FCS examined supported cumulus expansion in bovine cumulus-oocyte complexes, whereas the hamster complexes required at least 1.0% FCS to induce cumulus expansion. The addition of a serum filtrate, Solcoseryl, with BSA improved viability of the cumulus in the bovine but did not support cumulus expansion or completion of Meiosis I in bovine complexes. In vitro fertilization could be accomplished in media containing FCS by increasing the heparin concentration in the bovine system or reducing FCS for the hamster system. Polyspermy was increased when FCS was the protein supplement. It is not known whether this is an interaction of FCS with the sperm or oocyte. In conclusion, FCS was found necessary for follicle-stimulating-hormone (FSH)-induced cumulus expansion. It also improved cumulus cell viability and completion of the first meiotic division in complexes of both species compared with BSA.

Effect of free fatty acids on the concentration of free thyroxine in human serum: the role of albumin.

Abstract: The concentration of FFA in normal human plasma in vivo generally ranges between 02 and 07 meq/liter; slightly higher concentrations have occasionally been reported in patients who are seriously ill To determine whether such FFA concentrations may increase the concentration of free T4 in serum, we added increasing amounts of oleic acid to pooled normal human serum (with known FFA content) and measured free T4 by equilibrium dialysis Total FFA up to 3 meq/liter in normal serum, representing an FFA to albumin molar ratio of about 5:1, had little or no effect on the free T4 concentration, while higher FFA concentrations progressively increased free T4 This same molar ratio of FFA to albumin had to be exceeded to cause a significant increase in the free T4 concentration in diluted serum and in serum from patients with nonthyroid illness Serum from which more than 95% of the albumin had been removed by chromatography with Affi-Gel blue was much more sensitive to the effects of FFA on free T4 This enhanced sensitivity was reversed by readdition of albumin to the serum, and the addition of albumin to normal serum resulted in diminished effects of FFA on free T4 These results indicate the following: physiological concentrations of FFA do not significantly increase the free T4 concentration in normal human serum; when FFA reach supraphysiological concentrations in serum (in vitro) and the higher affinity FFA-binding sites on albumin become saturated (apparently at an FFA to albumin molar ratio of approximately 5:1), the excess FFA interact with other serum proteins, including thyroid hormone-binding globulin, and thereby increase the free T4 concentration; the concentration of albumin (or other FFA binders) must be considered when evaluating the observed effects of FFA To explore the relevance of these findings to the hypothesis that FFA may inhibit the binding of T4 to plasma proteins in patients with nonthyroid illness, we measured plasma FFA concentrations in 11 severely ill patients hospitalized in the intensive care unit We found a mean plasma FFA concentration of 045 +/- 011 (+/- SEM) mEq/liter and a mean serum albumin concentration of 239 +/- 029 g/dl in these patients Their mean plasma FFA to albumin molar ratio was 153 +/- 041 Since the FFA to albumin molar ratio must exceed about approximately 5:1 before a significant increase in the serum free T4 concentration occurs, these results suggest that FFA do not commonly influence the circulating free T4 concentration in vivo, even in severely ill patients

Direct evidence for the involvement of domain III in the N-F transition of bovine serum albumin.

Abstract: The domain III of bovine serum albumin containing residues 377-582 of the protein sequence was isolated and its behaviour in acid solution was studied. The fragment was found to undergo structural transformations over the pH range 3.5-4.5 known to cause N-F transition in serum albumin. On the other hand, an albumin fragment that was devoid of domain III was unable to exhibit such a transition. These results were consistent with a mechanism where N-F transition involves the separation of domain III from the rest of the albumin starts at about pH 4.3 and is completed at pH 3.5.

Monoclonal Antibodies to Plant Growth Regulators: III. Zeatinriboside and Dihydrozeatinriboside.

Abstract: Four high affinity monoclonal antibodies, which recognize two plant growth regulators from the cytokinin group, namely trans-zeatin riboside and dihydrozeatin riboside and their derivatives are reported. Six hybridomas were produced from three independent fusions of Balb/c spleen cells with P3-NS1-Ag 4-1 (abbreviated NS1) or X63-Ag 8.653 (X63) myeloma cells. The mice had been hyperimmunized with zeatin riboside-bovine serum albumin conjugate or dihydrozeatin riboside-bovine serum albumin conjugate for 3 months. The hybridomas secrete antibodies of the IgG 1 or IgG 2b subclass and allow the detection of femtomole amounts of the free cytokinins, their ribosides, and ribotides in plant extracts. The use of these monoclonals in radio- and enzyme-linked immunosorbent assay is also discussed.

Cellular promoters incorporated into the adenovirus genome: cell specificity of albumin and immunoglobulin expression.

Abstract: Recombinant adenoviruses were constructed in which the viral E1A gene was deleted and the E1B promoter was replaced by the rat albumin, mouse beta-major globin, or mouse immunoglobulin heavy-chain promoter. After infection of human or rat hepatoma cells, E1B-containing mRNAs could be detected only from the virus containing the albumin promoter. Conversely, only the immunoglobulin promoter was active in virus-infected myeloma cells. However, in hepatoma cells transcription from the albumin promoter in the virus was much less than that of the endogenous cellular albumin gene or of other viral genes. In primary mouse hepatocytes endogenous albumin gene transcription was high immediately after plating but declined within 24 h. Expression of the albumin promoter in the virus paralleled that of the cellular albumin gene. From these results it appears that cell-specific expression of albumin depends on the presence of tissue-specific trans-acting factors, but the presence of such factors does not suffice for a maximal rate of transcription, a conclusion that requires direct comparison within a differentiated cell of a newly introduced and preexisting active cell gene.

Obesity, non‐protein‐bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients

Abstract: This study attempted to determine the relationship of nutritional status, menopausal status, presence of breast cancer, stage of disease, and tumor estrogen receptor levels to percent non-protein-bound estradiol (%NPBE) and percent distribution of estradiol on sex hormone-binding globulin (SHBG) and albumin in breast cancer patients and control patients. Normal-weight controls had significantly lower %NPBE compared with overweight controls and normal-weight and overweight breast cancer patients. There was a significant shift in the percent distribution of estradiol from SHBG to albumin in breast cancer patients, independent of body weight. Elevated %NPBE and abnormal percent estradiol distribution on albumin persisted after mastectomy and were unrelated to menopausal status, presence and stage of disease, and tumor estrogen receptor levels. These results show that breast cancer patients have increased exposure to unbound circulating estradiol and an increased percentage of estradiol bound to albumin, which may influence the availability of estradiol, considering its low binding affinity to albumin. Because these abnormalities persist after mastectomy, the current results may be important in developing dietary intervention protocols that correct %NPBE and abnormal estradiol distribution on binding proteins.

Increased parathyroid hormone as a consequence of changed complex binding of plasma calcium in morbid obesity

Abstract: To evaluate whether changed plasma calcium binding might lead to a secondary increase of parathyroid hormone in morbid obesity, fasting measurements of serum ionized, ultrafiltrable and total calcium, calcium binding substances, and parathyroid hormone were undertaken in age- and sex-matched groups of obese (n = 44) and normal weight subjects (n = 52). The 24-hour urinary calcium excretion and clearance of creatinine were also measured. Calcium binding to proteins was changed. Serum total proteins and protein-bound calcium did not differ, but serum albumin was decreased in obesity. Consequently, obese subjects did not reveal the normal dependency of protein-bound calcium upon albumin. Calcium binding to other substances was also changed. Serum phosphate and bicarbonate were decreased, while the concentrations of citrate, lactate, acetoacetate, 3-hydroxybutyrate, free fatty acids, and urate were all increased, leaving the total concentration of plasma complex-bound calcium unchanged. Nevertheless, these reciprocal changes increase the concentrations of less readily reabsorbable anions in the renal ultrafiltrate. The changed pattern of calcium binding in serum of the obese subjects may serve to explain our findings of increased urinary calcium excretion, lowering of serum ionized calcium and increased parathyroid hormone levels, changes being significantly correlated with degree of overweight.

Serum albumin concentrations and oedema in the newborn.

Abstract: Serum albumin concentration was measured in 195 infants of 25 to 42 weeks' gestation during the neonatal period. Concentrations were significantly lower in preterm infants, rising from a mean of 19 g/l at 26 weeks to 31 g/l at term. There was a 15% increase in albumin concentrations in the first three weeks of life. Oedema in the early and late neonatal period was common in preterm infants but correlated poorly with hypoalbuminaemia. Measurement of serum albumin concentrations in preterm infants either routinely or because of oedema is not clinically useful.

Location of drug binding sites on human serum albumin.

Abstract: The location of Site I on the human serum albumin (HSA) molecule was investigated.Naphthol yellow- S (NY-S) was used as a representative ligand for Site I, since the bilirubin-displacing effect of NY-S was similar to that of Site I drugs such as warfarin and phenylbutazone.NY-S was bound to HSA with at least three classes of binding sites. The binding parameters of the primary class were one binding site (n1=1) and a binding constant (K1) of >107M-1, and the complex at equimolar ratio of dye to albumin exhibited metachromasy. The intrinsic fluorescence intensity, attributed to the single tryptophan residue (position 214), decreased significantly in this complex. Fragments A and C (residues 299-585 and 124-298, respectively, in the amino acid sequence of HSA) obtained by cyanogen bromide cleavage of HSA showed NY-S-binding ability.The binding of NY-S to fragment A or C aused the same metachromasy as seen with NY-S-HSA complex. Fragment C is markedly hydrophobic and contains the single tryptophan residue. The binding of NY-S to HSA was diminished by the chemical modification of lysine residues with pyridoxal 5'-phosphate (PLP). Further, lysine residues modified by PLP existed in fragment C.These results suggest that the primary binding site of NY-S, which corresponds to Site I, is located in the fragment C region of the HSA molecule.

An improved synthesis of a methotrexate-albumin-791T/36 monoclonal antibody conjugate cytotoxic to human osteogenic sarcoma cell lines.

Abstract: Improvements have been made in the synthesis of a drug-carrier-antibody conjugate using methotrexate as the drug, human serum albumin as the carrier, and a monoclonal antibody against a human osteogenic sarcoma cell line (791T/36). The improvements have resulted in a higher and more reproducible substitution of serum albumin by methotrexate, and improvements in the coupling of methotrexate covalently linked to human serum albumin to antibody resulting in a greater ease and efficiency of conjugation. The improvements have led to a conjugate of increased cytotoxicity while retaining the previously reported specificity. A conjugate is reported which shows cytotoxicity of 1.1 ng/ml (2.4 nm) with respect to methotrexate and 6 × 10-11m with respect to antibody in a clonogenic assay on 791T cells. This cytotoxicity is greater than that obtained using free methotrexate (2.8 ng/ml; 6.1 nm) and implies that drug cytotoxicity can be considered as the sum of drug uptake and the number of drug molecules required to kill a cell. This further suggests that antibodies could provide a potent delivery system for drugs which are poorly taken up by cells.

Free Fatty Acid Concentrations Correlated with the Available Fraction of Estradiol in Human Plasma

Abstract: A physiological in vivo increase of plasma free fatty acid concentration after an overnight fast was found to be accompanied by a rise of the non-protein bound estradiol fraction. A similar increase was observed after lipase activation by the i.v. injection of 500 IU heparin in 5 healthy non-fasting subjects. In vitro studies showed a direct relationship between non-protein bound estradiol and the concentration of linoleate, linolenate, and arachidonate both in undiluted serum and in Ringer's solution containing human serum albumin (45 g/liter). Moreover, the estradiol sex hormone binding globulin complex bound to a solid concanavalin A-Sepharose matrix was markedly dissociated by oleate and even more by linoleate, linolenate, or arachidonate. These results suggest that physiological diurnal elevations in plasma free fatty acids which are amplified by high fat consumption, obesity, and stress may imply major proportional increases of available estradiol, exerting a promotional effect on breast and endometrial cancer over the years.

Specificity of the human IgE response to inhaled acid anhydrides

Abstract: Patients with work-related respiratory symptoms caused by inhaled acid anhydrides (trimellitic (TMA), phthalic (PA), tetrachlorophthalic (TCPA), and maleic anhydrides) have specific IgE antibody. The antibody is specific for a conjugate of the sensitizing anhydride (the hapten) and human serum albumin (HSA). We have investigated the specificity of the reaction to determine whether the antibody is directed against (1) the anhydride, (2) new antigenic determinants formed by conjugation of albumin with the anhydride, or (3) the complete anhydride-HSA conjugate. For the patients sensitized to TCPA and TMA, RAST inhibition studies demonstrate the anhydride-HSA conjugate to be a more effective inhibitor of RAST than the sodium salt of the anhydride or an anhydride-bovine serum albumin conjugate, whereas for those sensitized to PA, the free hapten is almost as an effective inhibitor as the conjugate. With each sera HSA conjugates of anhydrides to which the patient is not sensitized are weaker inhibitors than the sensitizing anhydride-albumin conjugate. These results provide strong evidence that for the patients sensitized to TCPA and TMA, the antibody combines with the anhydride and the spatially adjacent portion of the HSA molecule, whereas in the patients sensitized to PA, the antibody is specific for the hapten.