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Biomedical subjects

Joseph W Cook

Publications and source records attributed to Joseph W Cook.

7 recordsLinked to original sources
PubMed2006

Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes.

Acetyl coenzyme A (acetyl-CoA) carboxylase isozyme 1 (ACC1) and acetyl-CoA carboxylase isozyme 2 (ACC2) are critical for de novo fatty acid synthesis and for the regulation of beta-oxidation. Emerging evidence indicates that one or both isozymes might be therapeutic targets for the treatment of obesity, type 2 diabetes, and dyslipidemia. One of the major obstacles in the field is the lack of readily-available source of recombinant human ACC enzymes to support systematic drug discovery efforts. Here, we describe an efficient and optimal protocol for expressing and isolating recombinant mammalian ACCs with high yield and purity. The resultant human ACC2, human ACC1, and rat ACC2 possess high specific activities, are properly biotinylated, and exhibit kinetic parameters very similar to the native ACC enzymes. We believe that the current study paves a road to a systematic approach for drug design revolving around the ACC inhibition mechanism.

Acetyl-CoA Carboxylase↗
PubMed2004

Size reduction ascending aortoplasty: is it dead or alive?

OBJECTIVE: Reduction ascending aortoplasty is a controversial procedure. Some believe that it can be appropriately applied when the anatomic features are favorable. Others suggest that it should be restricted to those patients who are at unacceptably high risk for more radical procedures, and there are also those who believe that reduction ascending aortoplasty should not be applied at all. The purpose of the article is to draw conclusions on the applicability of reduction ascending aortoplasty in modern cardiovascular surgery. METHODS: The issue was examined in the mirror of the authors' own experiences, by review and scrutiny of the literature available on the subject, and by conducting an extensive survey of the profession. RESULTS: We found that given proper indications (ie, poststenotic dilatations of <6 cm in diameter, absence of cystic medial necrosis, and a technique that decreases aortic diameter to <3.5 cm), nonreinforced reduction ascending aortoplasty performed concomitantly with aortic valve replacement appears to be a simple and safe procedure, with low morbidity and mortality and rare late complications. External reinforcement might extend the scope of indication for reduction ascending aortoplasty to ascending aortic aneurysms associated with aortic regurgitation and to those with primary structural aortic wall disease with comparable results. Experience also has shown that late complications might be further reduced by means of proper proximal anchoring and extending the wrap past the origin of the innominate artery. CONCLUSIONS: We conclude that reduction ascending aortoplasty is certainly alive. Although it does not appear to be an extremely popular operation, about half of the surgeons who responded believe it to be justified. Regardless of which modality is used, lifetime monitoring of ascending aortic size is essential and so advised. Because of recent sporadic reports of "under-the-wrap" aortic wall atrophy and rupture, the issue of reinforcement of reduction ascending aortoplasty requires continued re-evaluation.

Aorta↗
PubMed2004

The congenitally bicuspid aortic valve: how does it function? Why does it fail?

BACKGROUND: The study was intended to investigate the reason why congenitally bicuspid valves (CBAVs), which may function hemodynamically and clinically well, have a high early failure rate. METHODS: Observations were made on cryopreserved, then thawed human aortic roots containing CBAVs. Valvular function was studied in the left heart simulator using conventional and 500-frames/second cinematography, intravascular ultrasound, by preparation of silicone molds, and by computerized digital modeling. RESULTS: The function of the clinically "normal" CBAVs is characterized by (a). excessive folding and creasing, which (unlike in the trileaflet valve) persist throughout the cardiac cycle; (b). extended areas of leaflet contact; (c). significant morphologic stenosis; and (d). asymmetrical flow patterns and turbulence. CONCLUSIONS: The above features subject the CBAV to abnormally high stresses and may lead to early thickening and eventually calcification and stenosis. The abnormal flow patterns also predilect for dilatation and dissection of the ascending aorta.

Aortic Valve↗
PubMed2004

Morphological changes of the aortic valve leaflets in non-compliant aortic roots: in-vivo experiments.

BACKGROUND AND AIM OF THE STUDY: Age-related loss of elasticity of the naturally compliant aortic root disrupts the coordinated function of the valve leaflets. Morphological changes that developed over time in the aortic valve leaflets of non-compliant aortic roots were studied. METHODS: Stiffening of the aortic roots was achieved in vivo by applying Super Glue around the sinus of Valsalva in 27 New Zealand White rabbits. In nine animals, glue was applied only partially, and eight untreated rabbits served as controls. Histological evaluation of the aortic valves was performed at 8-11 months after surgery, and included immunohistochemistry and confocal microscopy with quantitative tissue assessment. Levels of collagen I, as a main component of fibrosis, and matrix metalloproteinases (MMP)-1 and MMP-9 and angiotensin-converting enzyme (ACE), as regulators of fibrosis, were analyzed. The morphological structure of the aortic valve leaflets was studied, and the length, thickness and area of leaflets were measured. RESULTS: Leaflects in all groups were found to be composed of a continuous layer of collagen fibers at the mural side, and loose connective tissue containing fibroblasts and few capillaries on the aortic luminal aspect. In stiffened aortic roots, the length and area of the leaflets were increased. The area occupied by collagen was elevated in non-compliant aortic root leaflets, but collagen fluorescence intensity was decreased, indicating less densely packed collagen fibers. Degradation and synthesis of collagen as reflected by MMP-1, MMP-9 and ACE levels was up-regulated. CONCLUSION: Loss of compliance in aortic roots leads to elongation of the leaflets which, combined with a decrease in collagen density, may render leaflets more susceptible to mechanical stress. In time, this may promote the development of degenerative changes in the aortic valve.

Animals↗
PubMed2003

Recovery of self-reported functional capacity after coronary artery bypass surgery.

STUDY OBJECTIVES: This study was conducted to determine the effects of age, gender, comorbid conditions, and exercise on the recovery of self-reported functional capacity after coronary artery surgery, and to identify predictors of 1-year functional capacity. PATIENTS: One hundred ninety-eight patients undergoing coronary artery bypass graft surgery. MEASUREMENTS AND RESULTS: Self-reported functional capacity was evaluated before surgery, and 3 months and 1 year postoperatively using the Veterans Specific Activity Questionnaire (VSAQ). Patients were classified into groups based on age, gender, comorbid conditions, and postoperative exercise. Repeated-measures analysis of variance was used to determine if groups differed with respect to functional capacity recovery and multiple linear regression was used to identify predictors of 1-year VSAQ score. A significant time by age interaction was found (p = 0.0001), with a more protracted recovery for older patients. There were significant group effects for gender (p = 0.0001), and presence of comorbid conditions (p = 0.0009); however, there were no time/group interactions for these variables. A significant group effect was found for postoperative exercise (p = 0.0001), with a trend toward group/time interaction (p = 0.096). Predictors of 1-year functional capacity were VSAQ score in the year prior to surgery and performance of regular aerobic exercise in the postoperative period. CONCLUSIONS: This study suggests that older patients attain good self-reported functional outcomes after surgery; however, the time course for recovery is more protracted than for younger patients. Functional capacity in the year prior to surgery and postoperative exercise are key predictors of 1-year functional capacity.

Activities of Daily Living↗
PubMedDate not supplied

Use of the SF36 general health status survey to document health-related quality of life in patients with coronary artery disease: effect of disease and response to coronary artery bypass graft surgery.

OBJECTIVE: The purpose of this study was to determine if the SF36 general health status survey has the sensitivity to detect physical function impairments before surgery and the expected improvement in health-related quality of life variables after elective coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, nonrandomized study design was used. OUTCOME MEASURES: The SF36 general health status survey comprises 36 multiple choice questions sorted into 8 categories, or subscales, that describe overall health status. The scores of this survey were used to measure the outcome. INTERVENTION: The SF36 was administered before surgery and at 12-month follow-up. Patients were also queried about the occurrence of angina with normal activities of daily living. RESULTS: Before surgery (n = 81), scores for all SF36 subscales (with the exception of mental health) were lower than published normative data, indicating the disease burden of coronary artery disease. At 12-month follow-up, scores in 6 of 8 subscales improved significantly; general health and role-emotional scores did not change. These changes in SF36 scores at follow-up paralleled a decreased occurrence of angina; before CABG surgery, 75% of patients (61 of 81) had angina; at 12-month follow-up, only 3.7% of patients (3 of 81) had angina. CONCLUSIONS: The SF36 can be used effectively to document changes in health-related quality of life variables in patients with coronary artery disease after CABG surgery.

Activities of Daily Living↗