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David Lee

Publications and source records attributed to David Lee.

106 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Current trends in urologic laparoscopic surgery.

PURPOSE: We examined the status of laparoscopy in urology and the impact of residency and fellowship training on the performance of laparoscopy as primary surgeon. We also examined whether performing nonsurgical tasks requiring two-handed dexterity had any link to the adoption of laparoscopic techniques by urologists. MATERIALS AND METHODS: A total of 8760 laparoscopy questionnaires containing 135 queries were mailed to urologists listed on the American Urological Association practicing urologists mailing list. The questions sought information on area of practice, time in practice, fellowship training, ambidexterity, laparoscopic experience, and experience with robotics. The response rate was 1.8% (155 of 8760). RESULTS: There appeared to be no significant correlation between the performance of laparoscopic surgery and participation in activities requiring bimanual dexterity. However, a correlation of strong statistical significance did exist between laparoscopic residency training and performance of laparoscopy after residency (p=0.003. There also was a correlation between fellowship training in laparoscopy/endourology and doing laparoscopy as primary surgeon. CONCLUSIONS: Participation in laparoscopic surgery during residency training is a major determining factor in performance of laparoscopy as a primary surgeon in practice. Younger surgeons trained in laparoscopy during residency are performing more laparoscopy post residency than those without laparoscopic training during residency. At present, there is a need to train more urologists in laparoscopy at the postgraduate level.

Adult↗

Determination of cell viability after laparoscopic tissue stapling in a porcine model.

BACKGROUND AND PURPOSE: Surgical stapling devices are often used to secure the distal ureter along with a cuff of bladder during laparoscopic nephroureterectomy. As the viability of cells within the stapled tissue would be important in patients with upper urinary-tract transitional-cell carcinoma, we determined the viability of cells within the lines of various commercially available staplers in a porcine model. MATERIALS AND METHODS: Four laparoscopic stapling devices were used: two vascular and two tissue designs (US Surgical, Norwalk, CT, and Ethicon, Cincinnati, OH). The devices were deployed across a portion of the bladder, much as they would be during a nephroureterectomy to create a bladder cuff while excising the distal ureter. The animals were sacrificed 6 weeks later, and the stapled sites were harvested for histopathologic examination by an experienced genitourinary pathologist (PH). RESULTS: Grossly, there were no visible staples at harvest of the stapled bladder and the ureterovesical junction, with a completely healed bladder being seen in all four animals. On histologic examination with hematoxylin and eosin staining, there were distinctly viable cells within the staple lines of the ureterovesical junction and the bladder wall, similar to the unstapled control tissue. There were viable cells in all samples of tissues stapled by either vascular or tissue staplers. CONCLUSIONS: Deployment of both vascular and tissue staplers resulted in viable cells within the staple lines at the ureterovesical junction and bladder wall in this porcine model. There is a potential risk of tumor recurrence at the stapled site in patients who have the ureter and bladder cuff secured with these devices during laparoscopic nephroureterectomy for upper-tract transitional-cell carcinoma. Despite this concern, to date, over a period of 13 years, clinical experience has not revealed a single case of tumor recurrence within the stapled cuff of bladder. Careful endoscopic evaluation of the stapled bladder-cuff site after laparoscopic nephroureterectomy should minimize the potential for local tumor recurrence.

Animals↗

Arc of buhler: incidence and diameter in asymptomatic individuals.

The purpose of this study was to determine the incidence and diameter of the Arc of Buhler by power injection digital subtraction angiography in asymptomatic patients. A retrospective evaluation of 120 combined celiac (CAx) and superior mesenteric artery (SMA) angiograms was carried out on potential live related liver transplant donors (asymptomatic patients) performed from January 1999 to May 2002. The diameter of the Arc of Buhler was calculated with reference to the 5 French catheters used to perform the diagnostic angiograms. It was considered hemodynamically significant if it preferential filled the branches of the other visceral vessel. An Arc of Buhler was identified in 4 patients (3.3%). All 4 patients had a patent gastroduodenal artery (GDA) and none of the 4 had a hemodynamically significant stenosis of either the SMA or the CAx. All Arcs of Buhler found measured less than 2.5 mm in diameter and half of them (2 of the 4) filled the CAx when power injecting the SMA and/or vice versa. There is a low incidence of Arc of Buhler in asymptomatic patients; however, 50% of those encountered were hemodynamically significant. When evaluating the Arc of Buhler by angiography in the setting of pathology, it is important to have a reference diameter and hemodynamic reference in the normal setting, particularly when the prospect of GDA ligation or embolization is entertained in the presence of CAx or SMA occlusion.

Adult↗

Cascading ecological effects of low-level phosphorus enrichment in the Florida everglades.

Few studies have examined long-term ecological effects of sustained low-level nutrient enhancement on wetland biota. To determine sustained effects of phosphorus (P) addition on Everglades marshes we added P at low levels (5, 15, and 30 microg L(-1) above ambient) for 5 yr to triplicate 100-m flow-through channels in pristine marsh. A cascade of ecological responses occurred in similar sequence among treatments. Although the rate of change increased with dosing level, treatments converged to similar enriched endpoints, characterized most notably by a doubling of plant biomass and elimination of native, calcareous periphyton mats. The full sequence of biological changes occurred without an increase in water total P concentration, which remained near ambient levels until Year 5. This study indicates that Everglades marshes have a near-zero assimilative capacity for P without a state change, that ecosystem responses to enrichment accumulate over time, and that downstream P transport mainly occurs through biota rather than the water column.

Animals↗