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)

Non-immobilised ligand interaction assay (NILIA) by CD spectroscopy provides an excellent technique to study molecular interactions in solution. Here are discussed molecular interactions of several systems that involve hosts and ligands with wide range of molecular sizes. Cytokine rhGM-CSF (14.6 kDa) bound to alpha-chain hGM-CSF receptor fragment (2 kDa, Kd = 35 microM), proline rich peptide (1.5 kDa) bound to fynSH3 domain (8 kDa, Kd = 28 microM), tumour imaging peptide (2 kDa) bound to mucin antigenic fragment (2 kDa, Kd = 20 microM), monoclonal antibody (150 kDa) bound to antigenic protein (120 kDa, Kd = 50 nM). Reconstitution of Cytochrome b5 (Cyt b5) from apo-Cyt b5 and hemin (Kd = 1.6 nM), correct protein folding of reconstituted porphobilinogen deaminase from apo-cofactorless form achieved using the product of the enzyme catalysis, preuroporphyrinogen, rather than porphobilinogen substrate. Competition studies of bound non-chiral drugs diclofenac and diazepam to carrier proteins such as HSA in the presence of fatty acids are few of the examples of the studies carried out by NILIA-CD spectroscopy. The CD changes in either backbone, aromatic side-chains and disulphide regions were used accordingly to screen qualitatively and quantitatively ligand binding in vitro. CD data were fitted by non-linear regression to the general equilibrium reaction of a single-binding site. NILIA-CD is fast compared to NMR, gives information on conformational changes due to interaction, avoids masking of the binding site due to immobilisation and requires no radiolabelling. NILIA-CD is thus an ideal technique for interaction, activity, screening studies.
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PMID:Biomolecules interactions and competitions by non-immobilised ligand interaction assay by circular dichroism. 978 30

Safety and bioavailability of pulmonary delivered interferon-beta 1a (IFN-beta1a, AVONEX, Biogen, Inc., Cambridge, MA) was evaluated in the nonhuman primate. Pulmonary bioavailability following intratracheal (i.t.) instillation of 50 microg/kg IFN-beta1a to rhesus macaques was approximately 10%. To evaluate pulmonary safety, IFN-beta1a was administered intrabronchially to rhesus and cynomolgus macaques at a dose of 60 microg/dose one, three, or seven times per week for 4 weeks. At scheduled termination, lungs were evaluated for gross and histomorphologic changes. IFN-beta1a or vehicle (human serum albumin [HSA] in phosphate-buffered saline [PBS]) treatment resulted in minimal to mild subchronic alveolitis, located primarily near the instillation sites. These responses were considered nonspecific and consistent with either instillation of a foreign protein or minor injury associated with the instillation procedure. In one rhesus macaque treated every day for 4 weeks, IFN-beta1a induced mild to moderate eosinophilic alveolitis, considered possibly an isolated type I hypersensitivity response to HSA or IFN-beta1a. Partial resolution of pulmonary lesions was seen in all recovery animals killed 2 weeks after cessation of treatment. In conclusion, this study shows that pulmonary administration of human IFN-beta1a is safe and that the pulmonary route of administration is a possible alternate route for the systemic delivery of IFN-beta1a.
J Interferon Cytokine Res 2002 Jun
PMID:Safety and systemic absorption of pulmonary delivered human IFN-beta1a in the nonhuman primate: comparison with subcutaneous dosing. 1216 83

We investigated the effects of either intravenous (IV) or intrabronchial (IB) treatment with transforming growth factor beta1 (TGF-beta1) during bacterial pneumonia in rats. Immediately following IB Escherichia coli inoculation (T0), animals (n=270) were randomized to receive a single treatment with human recombinant TGF-beta1 either via IV or IB, or via both IV and IB routes, or to receive placebo (human serum albumin, HSA) only. Blood and lung analysis was done at 6 and 168 h after E. coli inoculation. Other animals (n=40) were administered IV TGF-beta1 or HSA at T0 and 6, 12 and 24 h after E. coli inoculation to investigate the effects of multiple treatments also on survival rates alone. All animals received ceftriaxone daily. Route of administration did not influence TGF-beta1 (p=ns for the effect of TGF-beta1 comparing IV vs IB routes) and we averaged over this variable in analysis. The relative risk of death (mean +/- sem) was not altered by either single treatments administered at T0 (-0.18 +/- 0.25, p=0.47) or multiple treatments (0.40 +/- 0.50, p=0.66) of TGF-beta1. Single treatment with TGF-beta1 first decreased and then increased vascular leukocytes at 6 and 168 h, respectively, but increased alveolar leukocytes at both time points (p=0.02 comparing the differing effects of TGF-beta1 on vascular and alveolar leukocytes at 6 and 168 h). Although TGF-beta1 decreased blood and lung bacteria counts at 6 and 168 h, it also increased serum tumor necrosis factor levels and lung injury scores at these time points (p<0.05 for the effects of TGF-beta1 on each parameter at 6 and 168 h together). Thus, while increases in lung leukocyte recruitment with TGF-beta1 were associated with improved microbial clearance in this rat model of pneumonia, worsened lung injury may have negated these beneficial host defense effects, and overall survival was not significantly improved. Despite these harmful effects, additional studies may be warranted to better define the influence of exogenous TGF-beta1 on host defense during acute bacterial infections.
Cytokine 2003 Nov 21
PMID:TGF-beta1 increases microbial clearance but worsens lung injury during Escherichia coli pneumonia in rats. 1457 90

Growing evidence indicates that pro-inflammatory cytokines play a key role in alcoholic liver disease (ALD). This study investigates whether immune response toward oxidative stress-derived antigens could be involved in promoting cytokine production in alcohol abusers. Cytokine profile and circulating IgG against human serum albumin modified by malondialdehyde (MDA-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated in 59 heavy drinkers (HD) with (n=30) or without (n=29) ALD and 34 healthy controls. IgG against MDA-HSA and Ox-CL were significantly higher in HD with ALD than in HD without liver injury or healthy controls. The elevation of these antibodies was associated with higher circulating levels of IL-2 (p=0.005) and TNF-alpha (p=0.001), but not of IL-6 or IL-8. The prevalence of abnormal TNF-alpha was 5-fold higher in HD with oxidative stress-induced IgG than in those without. HD with the combined elevation of both TNF-alpha and oxidative stress-induced IgG had 11-fold (OR 10.7; 95%CI 1.2-97.2; p=0.023) greater risk of advanced ALD than those with high TNF-alpha, but no immune responses. Moreover, the combined elevation of TNF-alpha and lipid peroxidation-derived IgG was an independent predictor of ALD in HD. We propose that immune responses towards oxidative stress-derived antigen promote TNF-alpha production and contribute to liver damage in alcohol abusers.
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PMID:Immune responses against oxidative stress-derived antigens are associated with increased circulating tumor necrosis factor-alpha in heavy drinkers. 1846 Mar 46