Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A complete amino acid sequence has been determined for the UP1 single-stranded DNA binding protein from calf thymus that was first described by G. Herrick and B. M. Alberts [(1976) J. Biol. Chem. 251, 2124-2132]. Peptides required to establish the UP1 sequence were isolated by reversed-phase HPLC of digests produced by endoproteinase Lys-C, trypsin, chymotrypsin, Staphylococcus aureus V8 protease, and cyanogen bromide cleavage of UP1. The purified peptides were coupled to aminopolystyrene prior to solid-phase sequencing. UP1 contains 195 amino acids and has a molecular weight of 22,162. UP1 has a blocked NH2 terminus and contains a single NG,NG-dimethylarginine residue near its COOH terminus. Gas-phase sequencing of tryptic peptides derived from an analogous protein from mouse myeloma cells [Planck, S. R. & Wilson, S. H. (1980) J. Biol. Chem. 255, 11547-11556] revealed that this mouse helix-destabilizing protein shares a high degree of sequence homology with UP1. Of the 59 amino acids in the mouse protein that have so far been found to be homologous with UP1, 48 correspond exactly to sequences found in UP1. Most of the 11 differences that have been found between the sequences of these two proteins are conservative in nature, involving primarily the interchange of chemically similar amino acids. One 9-residue mouse sequence that is not obviously homologous to UP1 may be a result of the larger size of the mouse myeloma protein as compared to UP1. Since none of the UP1 or mouse myeloma helix-destabilizing protein sequence appears to be homologous to that of any previously sequenced protein, we presume that these two proteins represent a distinct class of single-stranded nucleic acid binding proteins that probably play a role in metabolism of single-stranded RNA or DNA in vivo.
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PMID:Amino acid sequence of the UP1 calf thymus helix-destabilizing protein and its homology to an analogous protein from mouse myeloma. 299 41

Objective laboratory tools are needed to monitor developing organ damage in sickle cell disease (SCD). Circulating endothelial cells (CECs) are indicative of vascular injury. We determined whether elevated CEC can be detected in asymptomatic SCD with the CellSearch system and whether the CEC count is related to clinical and blood-based biomarkers of disease severity. Fifteen consecutive clinically asymptomatic HbSS patients and 15 matched HbAA controls were analyzed for CEC counts, laboratory parameters of disease severity (Hb, leukocyte counts, HbF%), plasma levels of markers for endothelial activation (sVCAM-1, VWF:Ag) and of endogenous inhibitors of nitric oxide synthase (asymmetrical dimethylarginine [ADMA]). CEC counts were significantly higher in patients (12 cells/mL, IQR 8-29) as compared to controls (4 cells/mL, 3-10) (P=0.007). CEC counts were significantly higher in patients with pulmonary hypertension (PHT) (P=0.015), and increased with increasing number of affected organs (0-4 involved organs, P=0.002). No significant correlations between CEC and any other laboratory parameter were detected. In conclusion, CECs could prove to be an important new tool for assessing developing vasculopathy and organ damage in SCD.
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PMID:Circulating endothelial cells: a potential parameter of organ damage in sickle cell anemia? 1935 55

There is considerable evidence that oxidative stress and a loss of nitric oxide bioactivity are key mediators of the vasculopathies associated with sickle cell disease. A comprehensive nutraceutical strategy for mitigating the contribution of oxidative stress to pathogenesis - dubbed "full-spectrum antioxidant therapy" - may have utility in this syndrome. This strategy entails concurrent administration of phycocyanobilin - a phytochemical richly supplied by spirulina, shown to inhibit NADPH oxidase in a manner analogous to its chemical relatives biliverdin and bilirubin; high-dose folate - recently shown to quench peroxynitrite-derived radicals and restore coupling of NO synthase; N-acetylcysteine - for boosting intracellular glutathione levels; and a phase 2 inducer such as lipoic acid - to further promote glutathione synthesis while increasing expression of antioxidant enzymes. Suboptimal endothelial arginine levels, reflecting increased plasma arginase activity and elevated ADMA, contribute to the loss of NO bioactivity in sickle cell disease; supplementation with the arginine precursor citrulline may ameliorate this defect. Increased intakes of plant-derived nitrate have the potential to diminish the quenching of NO by plasma hemoglobin in sickle cell patients, while boosting systemic NO production independent of NO synthase activity. In addition to the well-documented utility of hydroxyurea - possibly a suboptimal strategy for life-long therapy owing to its mutagenic activity - rational pharmaceutical options for managing sickle cell disease include pentoxifylline and phosphodiesterase 5 inhibitors such as sildenafil.
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PMID:Potential utility of full-spectrum antioxidant therapy, citrulline, and dietary nitrate in the management of sickle cell disease. 2008 63