Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo

Complexes composed of peptide ligand for the serpin enzyme complex receptor covalently coupled to poly-L-lysine condensed by charge interaction with plasmid DNA direct gene transfer into receptor bearing cells. We compared intensity and duration of reporter gene expression in vitro and in vivo from serpin-enzyme receptor-directed gene transfer complexes prepared with poly-L-lysine of different chain lengths. When substituted with linker and ligand to comparable extents, DNA complexes containing short chain poly-L-lysine were larger and gave higher peak expression but significantly shorter duration of expression than those containing long chain poly-L-lysine. Both peak expression and duration of expression exceeded that observed with Lipofectin. Neither naked DNA nor DNA complexed with unsubstituted polylysine was effective in gene transfer. For in vivo experiments, complexes containing optimal ligand and degree of substitution (based on in vitro data, peptide C105Y, 11 ligands/plasmid DNA molecule) were prepared with either short chain or long chain polylysine and a beta-galactosidase expression plasmid. Following injection into the tail veins of mice, longer chain complexes gave significantly higher expression of reporter gene in lung and spleen that lasted for a significantly longer period of time than the shorter chain complexes. The short chain poly-L-lysine-DNA complexes were larger in diameter, as assessed by electron microscopy or atomic force microscopy, and gave less protection against DNase digestion in vitro than longer chain complexes. Thus, for gene transfer complexes directed at the serpin enzyme complex receptor, longer chain poly-L-lysine gave a much longer duration of expression both in vitro and in vivo. We speculate that this may be due to protection against degradation afforded the plasmid DNA by the tighter compaction produced by long chain poly-L-lysine.     

Implementation of the Anemia Guidelines

A study of 100 patients who made a severe suicide attempt suggested that the managed care criteria often applied for approving admission to hospitals for potentially suicidal patients were not, in fact, predictive of features seen in patients who actually made such attempts. Severe anxiety, panic attacks, a depressed mood, a diagnosis of major affective disorder, recent loss of an interpersonal relationship, recent abuse of alcohol or illicit substances coupled with feelings of hopelessness, helplessness, worthlessness, global or partial insomnia, anhedonia, inability to maintain a job, and the recent onset of impulsive behavior were excellent predictors of suicidal behavior. The presence of a specific suicide plan or suicide note were not. Patients with managed care were overrepresented by 245% in the study.     

Entorhinal cortex of aged subjects with Down''s syndrome shows severe neuronal loss caused by neurofibrillary pathology

OBJECTIVE: To examine directly the extent to which ICD-10 hyperkinetic disorder and DSM-IV attention-deficit/hyperactivity disorder (ADHD) identify the same children with the same difficulties. METHOD: Participants were children referred for symptoms of overactivity, inattention, and impulsivity, and a normal control group. Diagnostic criteria for ICD-10 hyperkinetic disorder and DSM-IV ADHD were applied retrospectively. Four groups were identified: hyperkinetic disorder and ADHD (n = 21), ADHD only (n = 22), clinic control (n = 15), and normal control (n = 19). The groups were compared on measures reflecting the central characteristics of ADHD, neurodevelopmental functioning, academic and cognitive functioning, and the presence of conduct problems. RESULTS: There is some evidence of increased symptom severity in the combined diagnostic group. Few differences emerged on measures of neurodevelopmental, academic, and cognitive functioning. Rates of conduct disturbance were similar in both ADHD groups. CONCLUSIONS: DSM-IV criteria identify a broader group of children than those identified by ICD-10. However, there is substantial overlap between the groups formed with these different criteria.