Biomedical subjects

Alex Lee

Publications and source records attributed to Alex Lee.

5 recordsLinked to original sources

PubMed2004

A single-amino-acid lid renders a gas-tight compartment within a membrane-bound transporter.

Proteins undergo structural fluctuations between nearly isoenergetic substates. Such fluctuations are often intimately linked with the functional properties of proteins. However, in some cases, such as in transmembrane ion transporters, the control of the ion transport requires that the protein is designed to restrict the motions in specific regions. In this study, we have investigated the dynamics of a membrane-bound respiratory oxidase, which acts both as an enzyme catalyzing reduction of O(2) to H(2)O and as a transmembrane proton pump. The segment of the protein where proton translocation is controlled ("gating" region) overlaps with a channel through which O(2) is delivered to the catalytic site. We show that the replacement of an amino acid residue with a small side chain (Gly) by one with a larger side chain (Val), in a narrow part of this channel, completely blocks the O(2) access to the catalytic site and results in formation of a compartment around the site that is impermeable to small gas molecules. Thus, the protein motions cannot counter the blockage introduced by the mutation. These results indicate that the protein motions are restricted in the proton-gating region and that rapid O(2) delivery to the catalytic site requires a gas channel, which is confined within a rigid protein body.

Amino Acids↗

PubMed2003

Personal watercraft injuries: 62 patients admitted to the San Diego County trauma services.

OBJECTIVE: To determine the types and patterns of injuries seen in personal watercraft (PWC) accidents. DESIGN: A retrospective review of medical records and imaging studies. SETTING: Level 1 and 2 trauma centers in San Diego County, California. PATIENTS/PARTICIPANTS: Trauma patients treated for PWC-related injuries between 1984 and 1997. MAIN OUTCOME MEASUREMENTS: Evaluation of injury patterns via chart review and imaging studies. INTERVENTION: None. RESULTS: A total of 62 patients were identified. The average age was 23 years (range 2-59 years). There were 41 males and 21 females. A total of 35 injuries (56%) involved another PWC. Of patients, 24 had loss of consciousness, with 8 closed head injuries. There were 17 chest injuries, with 10 pneumothoraces, and 16 lower extremity fractures (9 femur, 3 hip, 3 tibia-fibula, and 1 patella). CONCLUSIONS: Injuries related to PWC have increased dramatically over the past several years, becoming one of the leading causes of recreational water-sport injuries. This study supports a high level of awareness for significant blunt trauma to the chest and lower extremities in patients involved in PWC accidents.

Adolescent↗

PubMed2003

Percutaneous endoscopic gastrostomy. Procedure in practice.

Percutaneous endoscopic gastrostomy (PEG) is a relatively common procedure used in the treatment of children. As with all procedures, it must be used with care and only after taking careful account of circumstances and likely responses of the individual patient. This first of two articles on the procedure discusses the indications and contraindications for PEG insertion in children and then focuses on the procedure itself. The second article will discuss the role of the nurse as surgeon's assistant in the application of this procedure to children.

Child↗

PubMed2002

Ca(2+)-binding site in Rhodobacter sphaeroides cytochrome C oxidase.

Cytochrome c oxidase (COX) from R. sphaeroides contains one Ca(2+) ion per enzyme that is not removed by dialysis versus EGTA. This is similar to COX from Paracoccus denitrificans [Pfitzner, U., Kirichenko, A., Konstantinov, A. A., Mertens, M., Wittershagen, A., Kolbesen, B. O., Steffens, G. C. M., Harrenga, A., Michel, H., and Ludwig, B. (1999) FEBS Lett. 456, 365-369] and is in contrast to the bovine oxidase, which binds Ca(2+) reversibly. A series of R. sphaeroides mutants with replacements of the E54, Q61, and D485 residues, which form the Ca(2+) coordination sphere in subunit I, has been generated. The substitutions for the E54 residue do not assemble normally. Mutants with the Q61 replacements are active and retain the tightly bound Ca(2+); their spectra are not perturbed by added Ca(2+) or EGTA. The D485A mutant is active, binds to Ca(2+) reversibly, like the mitochondrial oxidase, and exhibits the red shift in the heme a absorption spectrum upon Ca(2+) binding for both reduced and oxidized states of heme a. The K(d) value of 6 nM determined by equilibrium titrations is much lower than that reported for the homologous D477A mutant of Paracoccus denitrificans or for bovine COX (K(d) = 1-3 microM). The rate of Ca(2+) binding with the D485A oxidase (k(on) = 5 x 10(3) M(-1) s(-1)) is comparable to that observed earlier for bovine COX, but the off-rate is extremely slow (approximately 10(-3) s(-1)) and highly temperature-dependent. The k(off) /k(on) ratio (190 nM) is about 30-fold higher than the equilibrium K(d) of 6 nM, indicating that formation of the Ca(2+)-adduct may involve more than one step. Sodium ions reverse the Ca(2+)-induced red shift of heme a and dramatically decrease the rate of Ca(2+) binding to the D485A mutant COX. With the D485A mutant, 1 Ca(2+) competes with 1 Na(+) for the binding site, whereas 2 Na(+) compete with 1 Ca(2+) for binding to the bovine oxidase. This finding indicates that the aspartic residue D442 (a homologue of R. sphaeroides D485) may be the second Na(+) binding site in bovine COX. No effect of Ca(2+) binding to the D485A mutant is evident on either the steady-state enzymatic activity or several time-resolved partial steps of the catalytic cycle. It is proposed that the tightly bound Ca(2+) plays a structural role in the bacterial oxidases while the reversible binding with the mammalian enzyme may be involved in the regulation of mitochondrial function.

Animals↗

PubMedDate not supplied

Effect of off-pump coronary artery bypass grafting on risk-adjusted and cumulative sum failure outcomes after coronary artery surgery.

BACKGROUND AND AIM: We have shown that cumulative sum (CUSUM) failure analysis may be more sensitive than standard statistical methods in detecting a cluster of adverse patient outcomes after cardiac surgical procedures. We therefore applied CUSUM, as well as standard statistical techniques, to analyze a surgeon's experience with off-pump coronary artery bypass grafting (OPCAB) and on-pump procedures to determine whether the two techniques have similar or different outcomes. METHODS: In 320 patients undergoing nonemergent, first time coronary artery bypass grafting, preoperative patient characteristics, rates of mortality and major complications, and ICU and hospital lengths of stay were compared between the on-pump and OPCAB cohorts using Fisher's exact tests and Wilcoxon two sample tests. Predicted mortality and length of stay were determined using previously validated models of the Cardiac Care Network of Ontario. Observed versus expected ratios of both variables were calculated for the two types of procedures. Furthermore, CUSUM curves were constructed for the on-pump and OPCAB cohorts. A multivariable analysis of the predictors of hospital length of stay was also performed to determine whether the type of coronary artery bypass procedure had an independent impact on this variable. RESULTS: The predicted mortality risk and predicted hospital length of stay were almost identical in the 208 on-pump patients (2.2 +/- 3.9%; 8.2 +/- 2.5 days) and the 112 OPCAB patients (2.0 +/- 2.2%; 7.8 +/- 2.1 days). The incidence of hospital mortality and postoperative stroke were 2.9% and 2.4% in on-pump patients versus zero in OPCAB patients (p = 0.09 and 0.17, respectively). Mechanical ventilation for greater than 48 hours was significantly less common in OPCAB (1.8%) than in on-pump patients (7.7%, p = 0.04). The rate of 10 major complications was 14.9% in on-pump versus 8.0% in OPCAB patients (p = 0.08). OPCAB patients experienced a hospital length of stay that was a median of 1.0 day shorter than on-pump patients (p = 0.01). The observed versus expected ratio for length of stay was 0.78 in OPCAB patients versus 0.95 in on-pump patients. On CUSUM analysis, the failure curve in OPCAB patients was negative and was flatter than that of on-pump patients throughout the duration of the study. Furthermore, OPCAB was an independent predictor of a reduced hospital length of stay on multivariable analysis. CONCLUSIONS: OPCAB was associated with better outcomes than on-pump coronary artery bypass despite a similar predicted risk. This robust finding was documented on sensitive CUSUM analysis, using standard statistical techniques and on a multivariable analysis of the independent predictors of hospital length of stay.

Aged↗