Showing papers on "Serum albumin published in 1989"
TL;DR: The three-dimensional structure of human serum albumin has been solved at 6.0 angstrom (A) resolution by the method of multiple isomorphous replacement and revealed the structure as a predominantly alpha-helical globin protein in which the course of the polypeptide can be traced.
Abstract: The three-dimensional structure of human serum albumin has been solved at 6.0 angstrom (A) resolution by the method of multiple isomorphous replacement. Crystals were grown from solutions of polyethylene glycol in the infrequently observed space group P42(1)2 (unit cell constants a = b = 186.5 +/- 0.5 A and c = 81.0 +/- 0.5 A) and diffracted x-rays to lattice d-spacings of less than 2.9 A. The electron density maps are of high quality and revealed the structure as a predominantly alpha-helical globin protein in which the course of the polypeptide can be traced. The binding loci of several organic compounds have been determined.
566 citations
TL;DR: It is speculated that C/EBP may play a general role in establishing and maintaining the differentiated, nonproliferative state.
Abstract: An expression vector capable of encoding full-length CCAAT/enhancer-binding protein (C/EBP) has been constructed and tested in transient transfection assays for its capacity to activate transcription from the promoter of the serum albumin gene When tested in cultured hepatoma cells, the C/EBP expression vector achieved potent trans-activation of the albumin promoter Less substantial activation was observed when the same experiment was conducted using cultured mouse fibroblasts Expression vectors that encoded defective forms of C/EBP failed to activate the albumin promoter Moreover, mutated variants of the albumin promoter that lack the C/EBP-binding site failed to be trans-activated The data are consistent with the interpretation that C/EBP is a bona fide transcription factor During the course of these experiments it was noted also that C/EBP is more than an order of magnitude less concentrated in cultured hepatoma cells than it is in adult liver cells Given these findings, we speculate that C/EBP may play a general role in establishing and maintaining the differentiated, nonproliferative state
433 citations
TL;DR: The strength of the association between serum albumin and mortality seems to be comparable with that for cigarette smoking and the associations persisted for cardiovascular disease and cancer even when deaths within the first five years of follow-up were excluded.
401 citations
TL;DR: Although many thousands of sera have been tested, deletion or gross alteration of the DBP gene has not been detected, lending support to the notion that such mutations might be lethal.
Abstract: Introduction UNLIKE other hydrophobic hormone-binding systems in mammalian plasma, the binding protein for vitamin D and its metabolites circulates in remarkably higher titer (5 × 10−6 M) compared to its major circulating ligand 25-hydroxycholecalciferol (25-OHD3) (5 × 10−8 M), and displays a rapid turnover rate (1) (see Table 1). Initially characterized as group-specific component or Gc-globulin, its identity with the plasma vitamin D binding protein (DBP) was discovered in 1975 (2). This hepatic protein has a strong homology with serum albumin (ALB) and α-fetoprotein (AFP) (3, 4). Although many thousands of sera have been tested, deletion or gross alteration of the DBP gene has not been detected, lending support to the notion that such mutations might be lethal. Since analbuminemia and abnormalities of other plasma binding proteins do not appear to cause disease (5–7), DBP activities are presumably vital. In recent years, new observations on the structure, origin, associations, and activities of DBP hav...
266 citations
TL;DR: The results showed a statistically significant decrease in the levels of GSH-Px, vitamins E, C and A, zinc, transferrin and albumin in the SDAT group, suggesting an alteration of free radical scavengers in the malnourished subgroup of theSDAT population could combine the radical and nutritional hypothesis advanced by some authors.
Abstract: Lipid peroxidation products and defenses against free radical damage were determined in serum of 55 patients with senile dementia of the Alzheimer type (SDAT) and compared with values in 24 age-matched healthy control subjects. The following parameters were evaluated: lipid-conjugated dienes and trienes, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in erythrocytes, vitamins E, C and A, zinc, selenium and copper, ceruloplasmin, transferrin and albumin. The results showed a statistically significant decrease in the levels of GSH-Px, vitamins E, C and A, zinc, transferrin and albumin in the SDAT group. On the other hand, most of the deficiencies concern the malnourished subgroup of the SDAT population (SOD, GSH-Px, vitamins E and C, selenium, zinc, transferrin and albumin). Such an alteration of free radical scavengers in the malnourished subgroup of the SDAT population could combine the radical and nutritional hypothesis advanced by some authors.
247 citations
TL;DR: An excellent parallelism between hydrolysis determined by a classical extraction method and that followed by direct and continuous spectrofluorometric recording of the monomer emission of pyrene is obtained.
246 citations
Journal Article•
TL;DR: It is concluded that nutritional status may represent a major determinant of survival in AIDS and the rate of albumin decrease may define a function limiting survival of individual patients with AIDS.
233 citations
TL;DR: Results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL).
202 citations
TL;DR: Tissue exudation and luminal transudation of two plasma markers, Evans blue (EB) dye and [125I]-human serum albumin (HSA), into the airways of the anesthetized guinea pig in response to platelet activating factor (PAF).
176 citations
TL;DR: Mild serum albumin depression and a more striking acute-phase protein elevation are greater in diabetes with microangiopathy, develop in glucose intolerance, and contribute substantially to elevated plasma viscosity in diabetes.
Abstract: Serum viscosity's increase in diabetes has been linked to the presence of microvascular sequelae and to changes in serum protein composition. The major change is a decline in albumin and an increase in the levels of acute-phase proteins. In this study, albumin and five acute phase proteins--alpha-1 acid glycoprotein, alpha-1 antitrypsin, haptoglobin, ceruloplasmin, and C-reactive protein--were measured. Levels in adult diabetes (principally type II) were compared with those in both subjects with glucose intolerance and control subjects (healthy subjects and nondiabetic ambulatory patients). Haptoglobin, alpha-1 acid glycoprotein, and C-reactive protein increased markedly in both diabetes and glucose intolerance; ceruloplasmin and alpha-1 antitrypsin increased more marginally. Serum albumin level decreased more strikingly as hyperglycemia advanced. Acute-phase proteins also increased in advanced glucose intolerance as in established diabetes. The acute-phase protein elevation did not differ with degree of control or duration of diabetes. When diabetics were divided into those with and without clinically detectable evidence of microvascular sequelae, elevation of haptoglobin, C-reactive protein and alpha-1 acid glycoprotein, and depression of albumin were found to progress with number of sequelae. The levels of these proteins, particularly haptoglobin, were also highly correlated with serum viscosity expressed as viscosity number. Mild serum albumin depression and a more striking acute-phase protein elevation are greater in diabetes with microangiopathy, develop in glucose intolerance, and contribute substantially to elevated plasma viscosity in diabetes.
174 citations
TL;DR: The results indicate that the large S protein may be the viral attachment protein for hepatocytes, binding directly to liver plasma membranes by its unique amino-terminal (pre-S1) sequence and to the amino acid sequence shared by the middle and large S proteins but not contained in the small S protein.
Abstract: Hepatitis B virus particles contain three related viral envelope proteins, the small, middle, and large S (surface) proteins All three proteins contain the small S amino acid sequence at their carboxyl terminus It is not clear which of these S proteins functions as the viral attachment protein, binding to a target cell receptor and initiating infection In this report, recombinant hepatitis B surface antigen (rHBsAg) particles, which contain only virus envelope proteins, were radioactively labeled, and their attachment to human liver membranes was examined Only the rHBsAg particles containing the large S protein were capable of directly attaching to liver plasma membranes The attachment was saturable and could be prevented by competition with unlabeled particles or by a monoclonal antibody specific for the large S protein In the presence of polymerized human serum albumin, both large and middle S protein-containing rHBsAg particles were capable of attaching to the liver plasma membranes Small S protein-containing rHBsAg particles were not able to attach even in the presence of polymerized human serum albumin These results indicate that the large S protein may be the viral attachment protein for hepatocytes, binding directly to liver plasma membranes by its unique amino-terminal (pre-S1) sequence These results also indicate that polymerized human serum albumin or a similar molecule could act as an intermediate receptor, attaching to liver plasma membranes and to the amino acid sequence (pre-S2) shared by the middle and large S proteins but not contained in the small S protein
TL;DR: The results of the experiments lead us to conclude that in domain 1 at least the histidines corresponding to the His C-2 proton resonances 1-5 play a dominant role in the N-B transition.
TL;DR: The effect of boswellic acids on bovine serum albumin (BSA)-induced arthritis in rabbits was studied and the leucocyte-inhibitory activity of bos wellic acids was not due to its cytotoxic effect.
Journal Article•
TL;DR: Immunohistochemical staining for albumin may be a useful technique for localizing blood-retinal barrier breakdown in diabetes, according to patients with no known ocular disease and those with various stages of diabetic retinopathy.
Abstract: Localization of the site of blood-retinal barrier breakdown in diabetes has been controversial. It has been particularly difficult to make assessments in clinical material where the use of tracer materials may not be practical. In this study, immunohistochemical staining for albumin was performed on paraffin-embedded eyes from patients with no known ocular disease and those with various stages of diabetic retinopathy. No extravascular albumin was detected in the retina or retinal pigment epithelium (RPE) of normal nondiabetics or diabetics with no ocular findings, but it was detected in 12.5% of mildly affected diabetics, 20% of background diabetic retinopathy cases, and 89% of proliferative diabetic retinopathy cases. The inner retinal vasculature appeared to be the primary site of leakage in diabetics because all cases demonstrating extravascular albumin-positivity expressed it in the inner retina. It usually permeated the vessel walls and spread along the inner surface of the retina. Some of these cases also contained albumin in the outer retina and RPE, suggesting that additional leakage also may occur through the RPE. A case of cytomegalovirus (CMV) retinitis showed albumin staining predominantly in the inner retina, whereas a rhegmatogenous retinal detachment showed only outer retina staining. These data suggest immunohistochemical staining for albumin may be a useful technique for localizing blood-retinal barrier breakdown.
TL;DR: The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated and a large variation was observed in the plasma concentration of midrazolam and between the plasma concentrations of the parent drug and its metabolite 1‐hydroxymethylmidazol am glucuronide.
Abstract: The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated. A large variation was observed in the plasma concentration of midazolam and between the plasma concentration of midazolam and its metabolite 1-hydroxymethylmidazolam glucuronide. The plasma albumin concentration governs the volume of distribution of midazolam. Decreased plasma albumin concentration (25 gm/L) results in an increased volume of distribution and a decreased elimination rate of midazolam. The observed plasma concentration ratio between the parent drug and its metabolite 1-hydroxymethylmidazolam glucuronide is governed by the variables of protein binding, the metabolic rate of midazolam, and the renal clearance of the glucuronide metabolite itself (which can be considered as a measure of the kidney function of the patient).
TL;DR: Experimental evidence is provided to indicate that the decreased content of heparan sulfate could cause some of the pathological findings in the blood vessels of animals with diabetes meflitus and proteoglycans appear to play an important regulatory function for plasma protein traffic across the capillary wall.
Abstract: Proteoglycans and glycosaminoglycans in the microenvironment are important regulators of various biological functions and contribute importantly to the organization of the molecular framework that exists in the basement membranes and associated connective tissue of various organs. Proteoglycans appear to regulate the passage of cells, glycoproteins, plasma proteins, and small ions from the luminal surface of blood vessels lined by endothelial cells to the surrounding connective tissue stroma. These molecules have also been shown to be present on the surface of cells where they have an important role in the regulation of cell to cell interaction, cell-substrate interaction and cell proliferation. l4 Furthermore, they have been shown to act as receptors for circulating factors such as growth factors and have been implicated in the secretion of various proteins from endothelial cell^.^.^ The capillary wall glycosaminoglycan composition has been shown to have an important regulator function for protein traffic across the capillary wall, particularly in kidney gl~meruli .~-~ The importance of heparan sulfate proteoglycans in maintaining normal renal glomerular function has been shown in experiments in which glomerular basement membranes have been treated with heparan sulfate degrading enzymes. Such experiments have shown that the removal of glycosaminoglycans is associated with increased permeability to femtin and to albumin.' Furthermore, the glomerular basement membranes of patients with the nephrotic syndrome have been shown to be almost completely deficient in heparan s ~ l f a t e . ~ * ' ~ There is also experimental evidence to indicate that the decreased content of heparan sulfate could cause some of the pathological findings in the blood vessels of animals with diabetes meflitus.'' Thus proteoglycans and glycosaminoglycans appear to play an important regulatory function for plasma protein traffic across the capillary wall. Changes in the composition of these vessel wall proteoglycans could conceivably result in alterations in this traffic. In this paper, evidence will be provided from experimental animals to illustrate four points:
Journal Article•
TL;DR: Capillary sealing phenomenon was shown to be independent of colloid osmotic pressure effect and is believed to be related to the size and the shape of the noncharged macromolecules.
TL;DR: In this paper, albumin and pre-transthyretin changes were compared in 40 patients managed with enteral and parental support with attainment of caloric/protein goals, using Rudolph's approach based on Shannon information measures.
Abstract: In this ongoing study, albumin and prealbumin (transthyretin) changes were compared in 40 patients managed with enteral and (or) parental support with attainment of caloric/protein goals. The concentration of prealbumin in serum changed rapidly and more accurately reflected current nutritional status of these patients than did that of albumin. We determined concentrations of albumin and prealbumin that reflected significant improvement in nutritional status, using Rudolph's approach based on Shannon information measures. Reference values for albumin and prealbumin in the treatment populations were 25 g/L and 107 mg/L, respectively. A prealbumin concentration of 135 mg/L or greater reflected a return to stable status.
Journal Article•
TL;DR: It is indicated that there is a role for vesicles in transendothelial cell transport and edema formation in animals with EAE, and horseradish peroxidase as a tracer correlated with the clinical course of EAE.
Abstract: Mechanisms involved in the loss of blood-brain barrier function in Lewis rats with experimental autoimmune encephalomyelitis (EAE) were examined using horseradish peroxidase (HRP) as a tracer. In animals injected with HRP before fixation, tracer was observed in two intracytoplasmic compartments: multivesicular bodies (presumably secondary lysosomes) and transcytotic vesicles. Quantitative morphometry of electron micrographs of capillary endothelial cells demonstrated a 5.2-fold increase in these vesicles. This increase in vesicular transport was associated with a decrease in mitochondrial content from 13.7% of the endothelial cytoplasmic area in the normal rat to 4.2% in EAE rats at the height of clinical disease. These alterations correlated with the clinical course of EAE. In animals infused with tracer after fixation, tracer was restricted to areas of cellular inflammation. Immunogold staining of endogenous albumin demonstrated the presence of albumin in cytoplasmic vesicles and in channel-like tubular structures adjacent to endothelial cell junctions. These results indicate that there is a role for vesicles in transendothelial cell transport and edema formation in animals with EAE.
Journal Article•
TL;DR: A quantitative autoradiographic method was developed to measure 111In-labeled proteins in extravascular tissues with a spatial resolution sufficient to associate these proteins with tissue morphology, and significantly higher average tissue concentrations were found in the infected thighs.
Abstract: A quantitative autoradiographic method was developed to measure 111In-labeled proteins in extravascular tissues with a spatial resolution sufficient to associate these proteins with tissue morphology. A linear relationship between measured grain density and isotope concentration was demonstrated with uniformly-labeled standard sources of epoxy-embedded gelatin containing [111In]albumin; half-distance of spatial resolution was 0.6 micron. The technique was illustrated by measuring 24-hr accumulation of diethylenetriaminepentaacetic acid-coupled 111In-labeled human polyclonal IgG and human serum albumin (HSA) in a thigh infection model in the rat. Gamma camera images localized the infection and showed target-to-background ratios of 2.5 +/- 0.3 for IgG and 1.4 +/- 0.02 for human serum albumin (mean +/- s.d., n = 3). Using quantitative autoradiography, significantly higher average tissue concentrations were found in the infected thighs at 4 to 4.5% of the initial plasma concentrations as compared to 0.2 to 0.3% of initial plasma concentrations in the noninfected thigh (p less than 0.05); these radiolabeled proteins were not inflammatory cell associated and localized primarily within the edematous interstitial spaces of the infection.
TL;DR: Measurement of soluble IL2R may have a role in the early diagnosis of acute rejection and in identifying patients with chronic rejection in whom further immunosuppression will provide no benefit.
TL;DR: This study corroborates previous reports of etoposide PB in normal human serum and demonstrates altered PB in patients with abnormal serum albumin or bilirubin levels.
Abstract: Etoposide plasma protein binding (PB) is reported to be 94% based on in vitro studies using normal human serum albumin (SA). Etoposide PB in 17 patients with cancer receiving etoposide (50 to 100 mg/m2) and in plasma of 14 volunteers was determined by equilibrium dialysis with 3H-etoposide. The unbound fraction (Fu) in patients with cancer was 0.139 +/- 0.099 compared with 0.043 +/- 0.0036 in plasma from normal volunteers (p less than 0.0009; t test). Etoposide binding ratio (BR) was correlated directly with SA (r2 = 0.83; p less than 0.05). In the population with cancer Fu was significantly correlated with bilirubin (r2 = 0.837; p less than 0.05). In a multivariate analysis, SA and bilirubin were significant predictors of Fu (r2 = 0.93; p less than 0.05). This study corroborates previous reports of etoposide PB in normal human serum and demonstrates altered PB in patients with abnormal serum albumin or bilirubin levels.
TL;DR: Increased endothelial permeability to solutes and water in inflammatory states is dependent on the shape and configuration of endothelial cells as determined by alterations in cytoskeletal elements, such as f-actin, and as regulated by intracellular second messengers such as free cytosolic calcium.
TL;DR: To investigate the association of age and albumin, albumin levels were determined in 241 apparently healthy subjects aged 55 to 101 and a small but consistent negative regression slope of about 4% per decade was found for those aged over 70.
Abstract: Some studies have shown a negative association between age and serum albumin. Several of these studies included older people with known disease. Disease may reduce albumin in any age group. Other studies have shown no association between age and albumin. To investigate the association of age and albumin, albumin levels were determined in 241 apparently healthy subjects aged 55 to 101. A small but consistent negative regression slope of about 4% per decade was found for those aged over 70. Because the relationship to age was small, the finding of hypoalbuminemia in an elderly patient generally should be attributed to disease rather than age alone.
Journal Article•
TL;DR: In this article, the authors showed that histone is an endogenous protein that is capable of transport through the blood-brain barrier (BBB) and may be a potential vector for pharmaceutical delivery through the BBB.
Abstract: The present studies were designed to determine if the endogenous cationic protein, e.g., histone, is capable of penetrating the blood-brain barrier (BBB) in vivo. Calf thymus histone was iodinated with [125I]iodine and was found to be taken up rapidly by isolated bovine brain capillaries used as an in vitro model system of the BBB via a time- and temperature-dependent mechanism. The binding was saturable and a Scatchard plot of the binding data was linear, yielding a KD = 15.2 +/- 2.8 microM and a maximal binding = 7.7 +/- 1.0 nmol/mg of protein. Other polycations such as protamine or polylysine markedly inhibited uptake of [125I] histone, but cationized albumin demonstrated minimal inhibition and cationized immunoglobulin caused no inhibition of bovine brain capillary uptake of [125I]histone. The in vivo brain VD of [125I] histone reached 159 +/- 70 microliters/g by 10 min of carotid arterial perfusion as compared to the 10-min VD for [3H]albumin, 17 +/- 7 microliter/g. Most of this uptake represented sequestration by the vasculature, but approximately 8% of the total histone taken up by brain was found to be transported unmetabolized (based on trichloroacetic acid precipitability of brain supernatant [( 125I]) into brain interstitium. These studies demonstrate that histone is transported through the BBB in vivo via absorptive-mediated transport. Thus, histone is an endogenous protein that is capable of transport through the BBB and may be a potential vector for pharmaceutical delivery through the BBB.
TL;DR: The plasma half life of recombinant human interleukin 1β (rhIL 1 β) was determined in rats by measuring the disappearance of the radioactivity of 125I‐labeled rhIL 1β from the circulation.
Abstract: The plasma half life of recombinant human interleukin 1 beta (rhIL 1 beta) was determined in rats by measuring the disappearance of the radioactivity of 125I-labeled rhIL 1 beta from the circulation. The plasma clearance showed a biphasic behavior: an initial fast disappearance (half life of about 3 min) was followed by a second slower one (half life of about 4 h). Twenty minutes after a single-dose injection of 125I-labeled rhIL 1 beta most of the radioactivity was concentrated in kidneys, liver and intestine. rhIL 1 beta induced the synthesis of alpha 1-acid glycoprotein (AGP), alpha 1-cysteine proteinase inhibitor (CPI) and beta-fibrinogen mRNA in liver. Half maximal stimulation was elicited by approximately 3000 U of rhIL 1 beta per animal. The mRNA changes for AGP and CPI were followed by corresponding protein increases in serum. Twenty hours after rhIL 1 beta injection, serum AGP rose from 0.7 to 2.5 mg/ml. CPI increased from 0.3 to 1.9 mg/ml 25 h after administration of rhIL 1 beta. Within 20 h after rhIL 1 beta injection, albumin serum concentration showed a strong decrease, preceded by a reduction in hepatic albumin mRNA levels. Neither changes in albumin synthesis nor degradation can explain this decrease suggesting that other mechanisms such as increased transvascular permeability are involved.
TL;DR: The time-dependent development of ionophore responsiveness by sperm exposed to capacitating conditions corroborates the idea that only capacitated cells can respond to undergo acrosomal loss in response to ionophores and suggests that albumin is not absolutely required for capacitation but is essential for the maintenance of motility.
Abstract: The kinetics of spontaneous and induced acrosomal loss have been studied in human sperm incubated in capacitating and noncapacitating media. Acrosomal status was quantitated using indirect immunofluorescence with a monoclonal antibody. The response of sperm to induction by calcium ionophores was time dependent reaching a maximum after 6 hours of incubation under capacitating conditions. The inducible population slowly decreased in size through the balance of a 24-hour incubation. The time-dependent development of ionophore responsiveness by sperm exposed to capacitating conditions corroborates the idea that only capacitated cells can respond to undergo acrosomal loss in response to ionophore. In contrast, only a small, constant percentage of sperm incubated under noncapacitating conditions responded to ionophore. Substitution experiments involving the addition or deletion of human serum albumin suggest that albumin is not absolutely required for capacitation but is essential for the maintenance of motility. Polyvinyl alcohol can be substituted for serum albumin, but it does not support capacitation or motility as well as HSA. These studies may provide a basis for optimizing capacitating conditions for human sperm in vitro as well as for diagnosing fertility or fertility potential based on measurements of spontaneous and ionophore induced acrosomal loss under defined culture conditions.
TL;DR: To explain the blunted diuresis and natriuresis in the presence of normal glomerular response to ANP, the possibility of an abnormality at post-glomerular level is investigated by studying ANP receptor density and affinity of the inner stripe of outer medulla and the inner medulla in ADR-and vehicle-treated rats.
TL;DR: Models of tryptophan catabolism and binding to serum albumin are presented to explain the observed effect of displacement of tryPTophan from albumin on the concentrations of free and bound tryptphan and on the rate of 5-hydroxytryptamine (5-HT) synthesis from tryptophile in the brain.
Abstract: Models of tryptophan catabolism and binding to serum albumin are presented to explain the observed effect of displacement of tryptophan from albumin on the concentrations of free and bound tryptophan and on the rate of 5-hydroxytryptamine (5-HT) synthesis from tryptophan in the brain. A rapid rate of dissociation of tryptophan from albumin (compared to the transit time of tryptophan through the liver) and a large fractional extraction of the free pool of tryptophan during passage through the liver are shown to be necessary factors in determining the effects observed. Because of the low fractional extraction of free tryptophan in the brain, the synthesis of 5-HT will be dependent only upon the free pool of tryptophan. Dissociation of tryptophan from albumin only causes a sustained increase in 5-HT synthesis in the brain because of the effect that this dissociation has on hepatic tryptophan catabolism and thereby on the free pool of tryptophan.
TL;DR: In a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days, and the free drug at a similar concentration did not significantly affect lesion size.
Abstract: Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the "scavenger" receptors present on macrophages and led to selective killing of intracellular Leishmania mexicana amazonensis amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.