Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isradipine (PN 200-110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl- and isopropylester, respectively). The binding of the (+)-(S)-isradipine and (-)-(R)-isradipine to isolated human serum albumin (HSA, 30 mumol/l) and alpha 1-acid glycoprotein (AAG, 10 mumol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06-20 mumol/l) using high-performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high-affinity binding sites on the AAG molecule (n(S) = 0.83 +/- 0.05, Ka(S) = (1.33 +/- 0.25) x 10(6) l/mol, n(R) = 0.85 +/- 0.07, Ka(R) = (1.17 +/- 0.44) x 10(7) l/mol). The (R)-enantiomer also exhibited an interaction with the secondary low-affinity binding sites (n'Ka'(R) = (2.66 +/- 0.65) x 10(4) l/mol). In contrast, the pharmacologically more potent (+)-(S)-enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 +/- 0.07, Ka(S) = (1.76 +/- 0.26) x 10(5) l/mol, nKa(R) = (3.62 +/- 0.06) x 10(4) l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10-80 ng/ml) at 37 degrees C was devoid of stereoselectivity.
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PMID:Stereoselective binding of isradipine to human plasma proteins. 779 94

In vitro mitoxantrone binding to human serum, human serum albumin (HSA, 600 microM) and alpha-1-acid glycoprotein (AAG, 15 microM) was investigated by ultrafiltration and the first-derivative spectrophotometry based on the "zero crossing" method. The binding of mitoxantrone to isolated proteins was studied at eight concentrations whose range depended on the protein used. The results showed that mitoxantrone binding to human plasma and HSA involved a saturable binding. The AAG binding involved a saturable binding followed by a non saturable process. Within the concentration range studied, the percent and binding parameters which characterize the drug-protein interaction were comparable in both methods.
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PMID:Comparison of the "zero crossing" method in derivative spectroscopy and ultrafiltration for the determination of free and bound fractions of mitoxantrone. 802 Aug 75

The interactions of camptothecin (CPT) and its derivatives (CPT-11 and SN-38) with human plasma proteins (serum albumin (HSA) and alpha 1-acid glycoprotein (alpha 1-AGP)) were studied mainly by means of ultraviolet and fluorescence spectroscopy. The binding constants of lactone ring-opened forms (A form) of CPT and CPT-11 with HSA were larger than those of the intact lactone forms (L form). In the case of SN-38, there was no difference in the constants between A form and L form. The binding constant of CPT (A form) with HSA was larger than those of CPT-11 and SN-38. The presence of cisplatin, which is presumed to be coadministered with CPT derivatives, did not affect the interaction of CPT derivatives with HSA. Only L form of CPT-11 among the CPT derivatives examined interacted with alpha 1-AGP, followed by quenching the fluorescence of alpha 1-AGP.
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PMID:[Interaction of camptothecin derivatives with human plasma proteins in vitro]. 848 59

The serum protein binding of itraconazole and fluconazole, new azole antifungal agents, has been investigated in vitro, in serum from healthy volunteers and from patients with cancer. Protein binding was determined by ultrafiltration. Concentrations of both alpha 1-acid glycoprotein (AAG) and albumin (HSA) were measured in all serum samples. The serum protein binding of itraconazole was reduced in patients (96.02 +/- 1.41% vs 97.25 +/- 0.54%; p < 0.01) with respect to healthy volunteers. In contrast, fluconazole protein binding was increased in the same group of patients (22.96 +/- 3.60% vs 13.30 +/- 2.58%; p < 0.01). HSA levels in cancer patients were significantly decreased (p < 0.01) and AAG levels were found to be significantly elevated in patients with respect to control subjects (p < 0.05). A significant linear relationship between the bound/unbound concentration ratio of itraconazole and HSA (r2 = 0.3340; p < 0.01) was found. Similarly, a significant relation was established between the bound/unbound concentration ratio of fluconazole and AAG levels (r2 = 0.2235; p < 0.05). Thus, a weak association between the binding of these drugs and serum protein levels has been observed. It is concluded that both antifungal drugs show different protein binding behaviour in cancer patients.
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PMID:Protein binding of itraconazole and fluconazole in patients with cancer. 855 24

P-selectin is a Ca(2+)-dependent lectin that participates in leukocyte adhesion to vascular endothelium and platelets. Myeloid cells and a subset of T lymphocytes express carbohydrate ligands at the cell surface. Previously, we suggested that heat stable antigen (HSA/mouse CD24), an extensively glycosylated cell surface molecule on many mouse cells, is a ligand for P-selectin. Here we show that HSA mediates the binding of monocytic cells and neutrophils to P-selectin. The monocytic cell lines ESb-MP and J774, peritoneal exudate cells, and bone marrow neutrophils could bind to lipopolysaccharide-activated bend3 endothelioma cells under rotation-induced shear forces and this binding was inhibited by mAb to P-selectin and HSA. Blocking was weak at room temperature but more efficient at 4 degrees C when integrin-mediated binding was decreased. Also the adhesion of neutrophils to stimulated platelets expressing P-selectin was blocked by HSA- and P-selectin-specific mAb. Latex beads coated with purified HSA from myeloid cells bound to activated endothelioma cells or platelets, and the binding was similarly blocked by mAb to P-selectin and HSA respectively. The HSA-coated beads were stained with P-selectin-IgG, very weakly with L-selectin-IgG but not with E-selectin-IgG. The staining was dependent on divalent cations and treatment with endoglycosidase F or neuraminidase indicated that sialylated N-linked glycans were recognized. The presence of these glycans was confirmed by biosynthetic labeling studies. Our data suggest that HSA, in addition to the recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to a group of monospecific P-selectin ligands on myeloid cells.
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PMID:Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. 856

Paired sera and cervicovaginal secretions (CVS) from 11 HIV-1- and 11 HIV-2-infected women, all clinically asymptomatic (CDC A1 and A2 categories), were analyzed for total IgG, IgA, albumin (HSA), IgG, and IgA antibodies to env-encoded surface glycoproteins of HIV-1 (gp160) and of HIV-2 (gp105), by comparison to 15 age-matched healthy controls. Secretion rates of IgG and IgA into CVS were evaluated by calculation of their relative coefficients of excretion (RCE) by reference to HSA. Cervicovaginal production of anti-HIV antibodies was evaluated by comparison between specific antibody activities of IgG and of IgA to HIV in CVS were, respectively, 6- and 4-fold increased, whereas the secretion rate of total IgG was 2.1-fold increased and that of total IgA was 2.5-fold reduced. In contrast, total IgG and IgA as well as their secretion rates were normal in HIV-2-infected women. In HIV-1- but not in HIV-2-infected women, HSA levels in cervicovaginal washings were twofold increased, demonstrating alteration of the mucosal barrier in HIV-1 infection. In HIV-1-infected patients, IgG and IgA to gp160 were detected in all sera and CVS. In HIV-2-infected patients, IgG to gp105 was detected in all sera and CVS, whereas IgA to gp105 could be detected in only half of sera and one-third of CVS. Cross-reactivity by IgG and/or IgA to HIV-1 or HIV-2 against the surface glycoprotein of the other HIV type was observed in sera as well as in CVS, and more frequently in HIV-2- than in HIV-1-infected women. Finally, the mean specific activities of IgG and of IgA to gp160 or gp105 were higher in CVS than in sera, evidencing a possible local synthesis of both isotypes in HIV-1 as well as in HIV-2 infections. As early as the asymptomatic stages, HIV-1 affects the cervicovaginal mucosa more than HIV-2 does, suggesting higher viral replication within the female genital tract in HIV-1 infection than in HIV-2 infection.
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PMID:Comparison of cervicovaginal humoral immunity in clinically asymptomatic (CDC A1 and A2 category) patients with HIV-1 and HIV-2 infection. 892 81

Five hybridomas producing human monoclonal antibodies (MAbs) of IgA and IgM isotypes reacting with the tumour associated TF antigen were generated after in vitro immunisation or antigen specific isolation of normal peripheral blood B cells using asialoglycophorin, a TF containing antigen. All 5 antibodies produced by the hybridomas bound strongly to asialoglycophorin and to synthetic glycoprotein containing the TF-epitope, with preference to the beta form (Galb1-3GalNAc-beta-O-CETE-BSA) as compared to the alpha form (Galbl-3GalNAc-alpha-O-APE-HSA) in ELISA. Flow cytometry analysis revealed binding to carcinoma cell lines of different origin such as breast, colon, pancreas, ovary, bladder, lung and, in addition, to some tumour cell lines of haematopoietic origin. Immunohistochemical analysis of tumour tissues revealed staining patterns typical for mucins, and the antibodies were found to bind to glycoproteins among the MUC-1 positive high m.w. fraction shed from a TF antigen positive ovarian carcinoma cell line.
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PMID:Human monoclonal antibodies specific for the tumour associated Thomsen-Friedenreich antigen. 898 92

The heat stable antigen (HSA, or murine CD24) is a glycosyl phosphatidylinositol-linked surface glycoprotein expressed on immature cells of most, if not all, major hematopoietic lineages, as well as in developing neural and epithelial cells. It has been widely used to stage the maturation of B and T lymphocytes because it is strongly induced and then repressed again during their maturation. Terminally differentiated lymphocytes, as well as most myeloid lineages, are negative for HSA. Erythrocytes are an exception in that they maintain high levels of HSA expression. HSA on naive B cells has been shown to mediate cell-cell adhesion, while HSA on antigen-presenting cells has been shown to mediate a costimulatory signal important for activating T lymphocytes during an immune response. Here, we characterize mice that lack a functional HSA gene, constructed by homologous recombination in embryonic stem cells. While T-cell and myeloid development appears normal, these mice show a leaky block in B-cell development with a reduction in late pre-B and immature B-cell populations in the bone marrow. Nevertheless, peripheral B-cell numbers are normal and no impairment of immune function could be detected in these mice in a variety of immunization and infection models. We also observed that erythrocytes are altered in HSA-deficient mice. They show a higher, tendency to aggregate and are more susceptible to hypotonic lysis in vitro. In vivo, the mean half-life of HSA-deficient erythrocytes was reduced. When infected with the malarial parasite Plasmodium chabaudi chabaudi, the levels of parasite-bearing erythrocytes in HSA-deficient mice were also significantly elevated, but the mice were able to clear the infection with kinetics similar to wild-type mice and were immune to a second challenge. Thus, apart from alterations in erythrocytes and a mild block in B-cell development, the regulated expression of HSA appears to be dispensable for the maturation and functioning of those cell lineages that normally express it.
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PMID:Altered erythrocytes and a leaky block in B-cell development in CD24/HSA-deficient mice. 902 39

During B cell genesis in mouse bone marrow (BM), precursor B cells pass through a series of developmental stages that have been defined by changes in expression of various marker molecules. The use of dissimilar phenotypic criteria in different laboratories, however, has led to the formulation of disparate models of B lymphopoiesis not fully reconciled with one another. We have directly compared two such models, one based on expression of intracellular mu heavy chain of IgM (c mu) and terminal deoxynucleotidyl transferase (TdT), the other monitoring cell surface leukosialin (CD43), heat-stable antigen (HSA; CD24) and the ectopeptidase BP-1. Each model uses cell surface B220 glycoprotein (CD45RA) to denote the B cell lineage. We have examined the cellular composition of four sorted BM fractions by immunofluorescent labeling of CD43, HSA and BP-1, using immunofluorescence microscopy of cytocentrifuged fractions to quantitate precursor B cell populations expressing either c mu or TdT. The results reveal a range of B cell differentiation stages within individual sorted BM fractions, providing a cross-reference between these two analytical methods and contributing to a unified model of B cell development in mouse BM.
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PMID:Two models of murine B lymphopoiesis: a correlation. 964 56

Previously we designed novel pseudotyped high-titer replication defective human immunodeficiency virus type 1 (HIV-1) vectors to deliver genes into nondividing cells (J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, S. Karlsson, and M. Schubert, Proc. Natl. Acad. Sci. USA 93:15266-15271, 1996). Since then we have made several improvements with respect to the safety, flexibility, and efficiency of the vector system. A three-plasmid expression system is used to generate pseudotyped HIV-1 particles by transient transfection of human embryonic kidney 293T cells with a defective packaging construct, a plasmid coding for a heterologous envelope (Env) protein, and a vector construct harboring a reporter gene such as neo, ShlacZ (encoding a phleomycin resistance/beta-galactosidase fusion protein), HSA (encoding mouse heat-stable antigen), or EGFP (encoding enhanced green fluorescent protein). The packaging constructs lack functional Vif, Vpr, and Vpu proteins and/or a large portion of the Env coding region as well as the 5' and 3' long terminal repeats, the Nef function, and the presumed packaging signal. Using G418 selection, we routinely obtained vector particles pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) with titers of up to 8 x 10(7) CFU/microgram of p24, provided that a functional Tat coding region was present in the vector. Vector constructs lacking a functional Tat protein yielded titers of around 4 x 10(6) to 8 x 10(6) CFU/microgram of p24. Packaging constructs with a mutation within the integrase (IN) core domain profoundly affected colony formation and expression of the reporter genes, indicating that a functional IN protein is required for efficient transduction. We explored the abilities of other Env proteins to allow formation of pseudotyped HIV-1 particles. The rabies virus and Mokola virus G proteins yielded high-titer infectious pseudotypes, while the human foamy virus Env protein did not. Using the improved vector system, we successfully transduced contact-inhibited primary human skin fibroblasts and postmitotic rat cerebellar neurons and cardiac myocytes, a process not affected by the lack of the accessory proteins.
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PMID:High-titer human immunodeficiency virus type 1-based vector systems for gene delivery into nondividing cells. 976 32


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