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.     

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.     

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.     

Characterization of Different Molecular Weight Fractions Separated from Utah Maltenes by Gel Permeation Chromatography

Maltenes derived from Utah bitumens were separated by gel permeation chromatography ( OPC) into fractions having number average molecular weights ( MW) in the range from 300 to 11985. The fractions were examined by vapor pressure osmometry, absorption spectrometry in the visible region as well as proton and carbon -13 NMR. The results are reported in comparison with those for the corresponding fractions separated from Athabasca maltenes. Utah fractions appeared to be more aliphatic with longer average aliphatic chains lengths. Branched and alicyciic types were more abundant in Utah samples, especially those with low MW, There was an apparent difference in the hydrocarbon structure of both Utah and Athabasca maltenes GPC     

Long-term hurricane risk assessment and expected damage to residential structures

This paper presents results from a study to evaluate long-term hurricane risks in the Southeastern United States using event-based simulation procedures. These risks are defined by (1) the statistical extreme wind climate, and (2) the expected insured losses from damage to residential structures. A probabilistic hurricane event model developed by the authors is used to evaluate long-term risks. The event model parameters were derived from a statistical analysis of storms affecting the Southeastern United States and include radius of maximum winds, central pressure difference, landfall location, storm track, and decay rate. The 50-year mean recurrence interval (MRI) gradient-level and surface gust wind speeds are evaluated for the region investigated using results from the simulation analysis. When coupled with a damage model, also developed by the authors, the results from the event-based simulation analysis are used to provide estimates of the expected losses. The states of North Carolina, South Carolina, and Florida are used to demonstrate the applicability of this procedure for evaluating expected losses. Implications for setting design wind speeds as well as risk-consistent insurance rates are discussed.     

The effect of asphaltene content on solvent selection for bitumen extraction by the SESA process

Bitumen is a complex mixture, containing a high proportion of poorly soluble asphaltenes. Unpredictable precipitation of this component can cause process problems during bitumen extraction. Consequently, the selection of an appropriate solvent is an important factor in the optimization of bitumen separation by solvent extraction. This aspect is discussed in the context of bitumen extraction from oil sands using the solvent extraction spherical agglomeration (SESA) process. The SESA process is a solvent extraction method which utilizes concurrent particle aggregation in order to overcome difficulties normally encountered in solid-liquid separation in the presence of fines.     

Use of extracorporeal life support for adult patients with respiratory failure and sepsis

Na+,K+-ATPase activity is abundant on the basolateral infoldings of the strial marginal cells and contributes to the maintenance of the characteristic electrolyte composition of the endolymph. However, the stria vascularis of the cochlea is known not to be innervated. In order to clarify its humoral regulation by serotonin, the K+-p-nitrophenylphosphatase activity of strial marginal cells was investigated with a cerium-based method in normal guinea pigs and in guinea pigs treated with reserpine, 5-hydroxytryptamine or reserpine plus 5-hydroxytryptamine. K+-p-nitrophenylphosphatase activity was almost completely depressed 3-20 days after reserpine administration. Ten days after reserpinization, followed by repeated 5-hydroxytryptamine treatment, the enzyme activity was detectable. These results suggest that 5-hydroxytryptamine increases the phosphatase activity. Thus, the function of the stria vascularis in producing cochlear endolymph may be regulated by 5-hydroxytryptamine.