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L Collins

Publications and source records attributed to L Collins.

108 records · Page 6Linked to original sources
PubMed1968

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Attitude of Health Personnel↗
PubMedDate not supplied

A small, synthetic peptide for gene delivery via the serpin-enzyme complex receptor.

BACKGROUND: The serpin-enzyme complex receptor (SECR) has previously been successfully targeted for gene delivery using synthetic peptide ligands covalently linked in fluid phase to commercially available polylysine preparations (approximately 10-54kDa). The objective of the present study was to improve this approach by the use of small, bifunctional, and easily standardised synthetic peptides. METHODS: Two synthetic peptides designated polylysine antitrypsin 1 (PAT1) (K16 FNKPFVFLI) and PAT2 (K16 CSIPPEVKFNKPFVFLI) were evaluated for gene delivery to the HUH7 human hepatocyte cell line. The K16 moiety binds DNA electrostatically, while the FVFLM motif of human alpha1-antitrypsin targets the SECR. RESULTS: Both PAT1 and PAT2 bind to and condense DNA into small particles as shown by laser scattering techniques. However, only PAT2 is effective for gene delivery, presumably on account of the greater distance between the K16 chain and the FVFLM motif. Gene delivery by PAT2/DNA complexes is chloroquine-dependent, can be blocked completely by free ligand (CSIPPEVKFNKPFVFLI), and is highly efficient (e.g. approximately five-fold more effective than lipofectamine). At physiological salt concentrations, PAT2/DNA complexes formed at 4 microg/ml DNA are approximately 350 nm in diameter and highly effective for gene transfer, but at 100 microg/ml DNA the complexes are aggregated (diameter > 4 microm) and inactive. CONCLUSIONS: A small (33 amino acid), bifunctional, synthetic peptide represents a highly efficient and readily standardised DNA vector for the SECR. The effectiveness of this peptide depends on the distance of the K16 moiety from the targeting ligand. High salt concentrations are not required to form effective vector/DNA complexes.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

A powerful cooperative interaction between a fusogenic peptide and lipofectamine for the enhancement of receptor-targeted, non-viral gene delivery via integrin receptors.

BACKGROUND: Following receptor-mediated endocytosis, vector/DNA complexes require assistance to exit endocytic vesicles in order to avoid degradation in the lysosomes. Overcoming this barrier is a major challenge for the development of receptor-targeted, non-viral gene delivery. METHODS: The fusogenic peptide of influenza virus haemagglutinin, lipofectamine and chloroquine were tested singly and in combination in various doses for promoting in vitro gene transfer by an integrin-targeted, non-viral DNA vector (polylysine-molossin). RESULTS: The fusogenic peptide and lipofectamine both individually promoted integrin-targeted gene delivery. However, the combined use of these agents was particularly effective, even at concentrations where neither agent singly had any effect on promoting gene delivery by polylysine-molossin. This optimal combination was effective on several cell lines and primary cell cultures. On the HuH7 cell line, it was approximately five-fold more effective than optimal chloroquine concentrations for integrin-targeted gene delivery and four to five times more effective than commercially available polyethylenimine. With the beta-galactosidase reporter gene, 60-65% of HepG2 cells and 75-80% of HuH7 cells were positive. The surface charge of polylysine-molossin/DNA/lipofectamine/fusogenic peptide complexes was approximately the same as that of polylysine-molossin/DNA complexes. The size distribution of the complexes suggested that competitive binding of polylysine-molossin and lipofectamine to DNA influenced the overall efficacy of this approach. CONCLUSIONS: Although the mechanisms are not clear, the combined use of very low doses of two membrane-destabilizing agents results in high levels of receptor-targeted gene delivery.

Amino Acid Motifs↗
PubMedDate not supplied

Enhancement of MR images using registration for signal averaging.

PURPOSE: With the advent of noninvasive neuroimaging, a plethora of digital human neuroanatomical atlases has been developed. The accuracy of these atlases is constrained by the resolution and signal-gathering powers of available imaging equipment. In an attempt to circumvent these limitations and to produce a high resolution in vivo human neuroanatomy, we investigated the usefulness of intrasubject registration for post hoc MR signal averaging. METHOD: Twenty-seven high resolution (7 x 0.78 and 20 x 1.0 mm3) T1-weighted volumes were acquired from a single subject, along with 12 double echo T2/proton density-weighted volumes. These volumes were automatically registered to a common stereotaxic space in which they were subsampled and intensity averaged. The resulting images were examined for anatomical quality and usefulness for other analytical techniques. RESULTS: The quality of the resulting image from the combination of as few as five T1 volumes was visibly enhanced. The signal-to-noise ratio was expected to increase as the root of the number of contributing scans to 5.2, n = 27. The improvement in the n = 27 average was great enough that fine anatomical details, such as thalamic subnuclei and the gray bridges between the caudate and putamen, became crisply defined. The gray/white matter boundaries were also enhanced, as was the visibility of any finer structure that was surrounded by tissue of varying T1 intensity. The T2 and proton density average images were also of higher quality than single scans, but the improvement was not as dramatic as that of the T1 volumes. CONCLUSION: Overall, the enhanced signal in the averaged images resulted in higher quality anatomical images, and the data lent themselves to several postprocessing techniques. The high quality of the enhanced images permits novel uses of the data and extends the possibilities for in vivo human neuroanatomy.

Artifacts↗
PubMedDate not supplied

A four-dimensional probabilistic atlas of the human brain.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

Adolescent↗
PubMedDate not supplied

L.A. County plans its disaster response.

The Los Angeles County Fire Department is one of many agencies making great strides in the development of urban search and rescue programs. Much of the department's USAR training, equipment, and strategies have been tested on real incidents. Each incident presents new challenges and teaches new lessons. Before the establishment of the three-tiered USAR system, those personnel nearest an incident handled it. Many never saw a similar incident again. The lessons they learned were often lost because there was no system to collect their experiences, retrieve the information, and make it available to other emergency responders in the form of training programs. A major advantage of tiered response is the system's ability to ensure rapid response by trained, experienced, and well-equipped personnel. Rather than repeating mistakes and forgetting successful rescue methods, the system allows the retrieval of the experiences of personnel and their use in the development of training materials. Urban search and rescue specialists have the ability to build on earlier experiences to raise the overall level of skills. The net result is more effective training, increased efficiency, and enhanced safety for rescuers and victims. The field of urban search and rescue is still in its infancy. Many new and innovative strategies, techniques, and tools are on the horizon. In recent years, there has been growing interest in this specialty across the nation. We expect this trend to continue as breakthroughs occur. More than ever, it is important for all concerned agencies to share information and to work together to improve our ability to save lives.

Disaster Planning↗