The use of nonhomologous scatchard analysis in the evaluation of ligand-protein interactions

Scatchard plots are widely used for the graphical presentation of receptor-ligand binding data. When a combination of labelled and unlabelled ligand molecules is used in a binding assay, equations for Scatchard plots are readily available if the labelled and unlabelled ligands have similar binding affinities. In this article, Everardus van Zoelen, Roel Kramer, Herman van Moerkerk and Jacques Veerkamp present mathematical equations to obtain the binding characteristics of an unlabelled ligand in a Scatchard plot, which has a dissociation equilibrium constant different from that of the labelled ligand used.     

Managing the uncertainties of low-level radioactive waste disposal

A special program developed by the authors, called Pombe, identifies protein coding regions in the Schizosaccharomyces pombe genome. Linear discriminant analysis was applied to predict 5'-terminal, internal, 3'-terminal exons (coding-exon) and introns. The accuracy of the prediction was tested by cross verifications. The sensitivity, specificity and correlation coefficient for the internal exon prediction were 98.5%, 99.9% and 98.3% respectively at the nucleotide level. Open reading frames were studied and used to predict intron-less genes: 99.0% of such genes were identified with correct stopping sites. The gene structure was determined by dynamic programming and the prediction achieved 97.0% correlation coefficient at the nucleotide level. The program is available at http:(/)/clio.cshl.org/genefinder.     

Serum endothelin and atrial natriuretic peptide in cirrhotic patients with ascites and hepatorenal syndrome

BACKGROUND: The pathogenesis of cirrhotic ascites and hepatorenal syndrome remains unresolved. The involvement of both endothelin-1 and atrial natriuretic peptide have recently been suggested. This study investigated the concentrations of serum endothelin and atrial natriuretic peptide in cirrhotic patients. METHODS: Seven healthy subjects and 31 cirrhotic patients were studied. Cirrhotic patients were divided into three groups: Group I, 16 cirrhotic patients without ascites; Group II, 10 cirrhotic patients with ascites, but without hepatorenal syndrome; and Group III, five cirrhotic patients with hepatorenal syndrome and ascites. Their sera were analyzed for endothelin-1 and atrial natriuretic peptide concentrations. RESULTS: Cirrhotic patients with ascites, Group II and Group III, had higher plasma endothelin-1 concentrations (15.9 +/- 2.3 pg/ml and 24 +/- 2.1 pg/ml, respectively) than normal subjects and compensated cirrhotics (3.8 +/- 0.7 pg/ml and 6.4 +/- 1.1 pg/ml, respectively); p < 0.001). Atrial natriuretic peptide concentrations were also significantly higher in cirrhotic patients than in normal subjects (p < 0.025). Plasma endothelin-1 concentration had a negative correlation with creatinine clearance (r = -0.65, p < 0.001), as did atrial natriuretic peptide concentrations (r = -0.44, p = 0.012). Plasma endothelin-1 correlated significantly with atrial natriuretic peptide concentrations (r = 0.38, p = 0.035). CONCLUSIONS: Both endothelin-1 and atrial natriuretic peptide concentrations were elevated in cirrhotic patients with ascites and hepatorenal syndrome. Endothelin-1 may have a negative impact on renal function. Our data also suggested that impaired responsiveness rather than impaired secretion of atrial natriuretic peptide is responsible for sodium retention in cirrhotic patients with ascites.     

Plasma folic acid cutoff value, derived from its relationship with homocyst(e)ine

We established the cutoff value for plasma folic acid, using plasma homocyst(e)ine as the functional marker. To do this, we investigated the relationship of the plasma folic acid of 103 apparently healthy adults with their fasting plasma homocyst(e)ine and with their plasma homocyst(e)ine 6 h after oral methionine challenge (100 mg/kg). We also studied the relationship of their plasma folic acid with the decline of fasting plasma homocyst(e)ine after 7 days of folic acid supplementation (5 mg/day). The three approaches suggested a cutoff value of 10 nmol/L. The chances of individuals to significantly (P <0.05) lower their plasma homocyst(e)ine after folic acid supplementation proved significantly higher at plasma folic acid concentrations < or = 10 nmol/L, as compared with folic acid concentrations above this value (odds ratio, 5.02; 95% confidence interval, 1.87-13.73). We suggest adopting a 10 nmo/L plasma folic acid cutoff value on functional grounds.