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David Lee

Publications and source records attributed to David Lee.

8 recordsLinked to original sources
PubMed2026

Genomic and Phenotypic Characterization of Two Novel Enterobacter Phages With EDTA-Enhanced Antibiofilm Activity.

Multidrug-resistant members of the Enterobacter cloacae complex (ECC) are increasingly linked to difficult-to-treat infections and biofilm-mediated antimicrobial tolerance. Here, two lytic phages, vB_EhoIP_HHH and vB_EluM_RZH, displaying podovirus-like and myovirus-like morphology, respectively, were isolated from the River Chelt. HHH has a 39,582 bp genome (51.2% GC, 63 ORFs), while RZH has a 174,197 bp genome (39.4% GC, 314 ORFs), with neither genome carrying antimicrobial resistance, virulence or lysogeny-associated genes. VIRIDIC and VICTOR analyses placed HHH within Kayfunavirus and RZH within Karamvirus, supporting their classification as distinct species. Both phages demonstrated rapid adsorption, short latent periods and stability across physiological pH and temperature ranges. A phage cocktail targeting MDR ECC strain was evaluated with EDTA against established biofilms. Crystal violet assays showed the greatest biomass reduction at MOI 10 with 0.5-0.75 mM EDTA. Bliss independence analysis revealed localized synergy within this window but significant overall antagonism at higher EDTA concentrations. CFU enumeration confirmed greater activity against 24 h than 48 h biofilms. The optimized combination also reduced recoverable bacteria in a fibroblast infection model while maintaining low LDH release. These findings identify two novel lytic Enterobacter phages and support a narrow EDTA concentration window for enhanced phage-mediated antibiofilm activity.

Biofilms↗
PubMed2002

Fibrillin: from microfibril assembly to biomechanical function.

Fibrillins form the structural framework of a unique and essential class of extracellular microfibrils that endow dynamic connective tissues with long-range elasticity. Their biological importance is emphasized by the linkage of fibrillin mutations to Marfan syndrome and related connective tissue disorders, which are associated with severe cardiovascular, ocular and skeletal defects. These microfibrils have a complex ultrastructure and it has proved a major challenge both to define their structural organization and to relate it to their biological function. However, new approaches have at last begun to reveal important insights into their molecular assembly, structural organization and biomechanical properties. This paper describes the current understanding of the molecular assembly of fibrillin molecules, the alignment of fibrillin molecules within microfibrils and the unique elastomeric properties of microfibrils.

Animals↗
PubMed2002

Totally endoscopic management of upper tract transitional-cell carcinoma.

BACKGROUND AND PURPOSE: Nephron-sparing therapy arose spurred by efforts to delay dialysis for patients with renal insufficiency or solitary kidneys. As technology has improved, complete endoscopic ablation of tumor via the holmium and Nd:YAG lasers has proven efficacious for cancer control. We have extended ureteroscopic treatment to patients with normal contralateral kidneys given the proper indications. For required extirpative therapy in cases of uncontrolled cancer, laparoscopic nephroureterectomy is rapidly becoming popular and appears to lend the same tumor control as open surgery while significantly lessening morbidity. We reviewed our experience with endourologic treatment and propose an algorithm for the management of upper tract TCC. PATIENTS AND METHODS: Over the period from August 1998 to May 2000, 70 patients underwent ureteroscopic evaluation, treatment, or both for TCC. During the same period, 24 patients had a hand-assisted laparoscopic nephroureterectomy (HALNU) performed. A thorough chart review was performed to determine pathologic data and management decision-making. RESULTS: Of the 70 patients evaluated ureteroscopically, 46 were examined for the first time, while the remaining 24 patients were already on the surveillance protocol. Of the 46 initially evaluated patients, 18 were referred for HALNU. Fifteen other patients were placed on surveillance. Of the 24 patients already on surveillance, only 1 required HALNU. The most common reasons for nephroureterectomy were bulky tumors that were ureteroscopically unresectable, high-grade disease, and patient preference. CONCLUSIONS: The combination of ureteroscopy and laparoscopy has made the management of upper tract TCC totally endoscopic, providing decreased morbidity while maintaining cancer control.

Algorithms↗
PubMed2002

Current management of urolithiasis: progress or regress?

PURPOSE: To assess the impact of the development of less powerful second- and third-generation shockwave lithotripters on surgical stone therapy in light of recent advances in ureteroscopy and laser lithotripsy. As such, we sought to identify current trends in the treatment of stone disease, both at our university medical center and nationally, and to contrast them with the corresponding data from 1990. PATIENTS AND METHODS: All urolithiasis procedures (ureteroscopy, SWL, open surgery, and percutaneous stone removal) performed in 1998 were compared with all urolithiasis procedures performed 8 years earlier (1990) at a single institution (Washington University, St. Louis). In addition, Medicare data for each year from 1988 through 2000 were collected from the Health Care Financing Administration to assess the national trends for open stone surgery, ureteroscopic stone removal, SWL, and percutaneous nephrolithotomy. RESULTS: At Washington University, the number of percutaneous stone removals remained stable; however, the overall number of ureteroscopies increased by 53%, while the number of SWLs, decreased by 15%. The Medicare data likewise reflect a marked decrease in open stone surgery and a marked increase in ureteroscopic stone surgery with a slight increase in SWL. Utilization of percutaneous nephrolithotomy remained unchanged. CONCLUSIONS: We believe this trend toward ureteroscopy is attributable to several factors: improved, smaller rigid and flexible ureteroscopes; the availability of more effective intracorporeal lithotripters (e.g., pneumatic and holmium laser), and the lack of development of lower cost, more effective SWL. This is an unfortunate trend, as we are moving away from the noninvasive treatment that was the hallmark of urolithiasis therapy at the beginning of the last decade toward more invasive endoscopic therapy. Increased research efforts in SWL technology are sorely needed.

Female↗
PubMed2002

Gene3D: structural assignment for whole genes and genomes using the CATH domain structure database.

We present a novel web-based resource, Gene3D, of precalculated structural assignments to gene sequences and whole genomes. This resource assigns structural domains from the CATH database to whole genes and links these to their curated functional and structural annotations within the CATH domain structure database, the functional Dictionary of Homologous Superfamilies (DHS) and PDBsum. Currently Gene3D provides annotation for 36 complete genomes (two eukaryotes, six archaea, and 28 bacteria). On average, between 30% and 40% of the genes of a given genome can be structurally annotated. Matches to structural domains are found using the profile-based method (PSI-BLAST). and a novel protocol, DRange, is used to resolve conflicts in matches involving different homologous superfamilies.

Animals↗
PubMed2002

The CATH extended protein-family database: providing structural annotations for genome sequences.

An automatic sequence search and analysis protocol (DomainFinder) based on PSI-BLAST and IMPALA, and using conservative thresholds, has been developed for reliably integrating gene sequences from GenBank into their respective structural families within the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath_new). DomainFinder assigns a new gene sequence to a CATH homologous superfamily provided that PSI-BLAST identifies a clear relationship to at least one other Protein Data Bank sequence within that superfamily. This has resulted in an expansion of the CATH protein family database (CATH-PFDB v1.6) from 19,563 domain structures to 176,597 domain sequences. A further 50,000 putative homologous relationships can be identified using less stringent cut-offs and these relationships are maintained within neighbour tables in the CATH Oracle database, pending further evidence of their suggested evolutionary relationship. Analysis of the CATH-PFDB has shown that only 15% of the sequence families are close enough to a known structure for reliable homology modeling. IMPALA/PSI-BLAST profiles have been generated for each of the sequence families in the expanded CATH-PFDB and a web server has been provided so that new sequences may be scanned against the profile library and be assigned to a structure and homologous superfamily.

Algorithms↗
PubMed2002

The CATH protein family database: a resource for structural and functional annotation of genomes.

Over the last decade, there have been huge increases in the numbers of protein sequences and structures determined. In parallel, many methods have been developed for recognising similarities between these proteins, arising from their common evolutionary background, and for clustering such relatives into protein families. Here we review some of the protein family resources available to the biologist and describe how these can be used to provide structural and functional annotations for newly determined sequences. In particular we describe recent developments to the CATH domain database of protein structural families which have facilitated genome annotation and which have also revealed important caveats that must be considered when transferring functional data between homologous proteins.

Databases, Protein↗