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Biomedical subjects

Thomas H Lee

Publications and source records attributed to Thomas H Lee.

At least 19 recordsLinked to original sources
PubMed2005

Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation.

Rip1 is required for IkappaB kinase activation in response to tumor necrosis factor alpha (TNF-alpha) and has been implicated in the Toll-like receptor 3 (TLR3) response to double-stranded RNA. Cytokine production is impaired when rip1-/- cells are treated with TNF-alpha, poly(I-C), or lipopolysaccharide, implicating Rip1 in the Trif-dependent TLR3 and TLR4 pathways. To examine the role of Rip1 in the Trif-dependent TLR4 pathway, we generated rip1-/- MyD88-/- cells. Lipopolysaccharide failed to stimulate NF-kappaB activation in rip1-/-MyD88-/- cells, revealing that Rip1 is also required for the Trif-dependent TLR4-induced NF-kappaB pathway. In addition to activating NF-kappaB, TLR3/4 pathways also stimulate interferon regulatory factor 3 activation. However, we find that Rip1 expression stimulates NF-kappaB but not interferon regulatory factor 3 activity. In the TNF-alpha pathway, Rip1 interacts with the E3 ubiquitin ligase Traf2 and is modified by polyubiquitin chains. Upon TLR3 activation, Rip1 is also modified by polyubiquitin chains and is recruited to TLR3 along with Traf6 and the ubiquitin-activated kinase Tak1. These studies suggest that Rip1 uses a similar, ubiquitin-dependent mechanism to activate IkappaB kinase-beta in response to TNF-alpha and TLR3 ligands.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Bioluminescence regenerative cycle (BRC) system: theoretical considerations for nucleic acid quantification assays.

A novel application of bioluminescence for nucleic acid quantification, the bioluminescence regenerative cycle (BRC), is described in theoretical terms and supported by preliminary experimental data. In the BRC system, pyrophosphate (PPi) molecules are released during biopolymerization and are counted and correlated to DNA copy number. The enzymes ATP-sulfurylase and firefly luciferase are employed to generate photons quantitatively from PPi. Enzymatic unity-gain positive feedback is implemented to amplify photon generation and to compensate for decay in light intensity by self-regulation. The cumulative total of photons can be orders of magnitude higher than in typical chemiluminescent processes. A system level theoretical model is developed, taking into account the kinetics of the regenerative cycle, contamination, and detector noise. Data and simulations show that the photon generation process achieves steady state for the time range of experimental measurements. Based on chain reaction theory, computations show that BRC is very sensitive to variations in the efficiencies of the chemical reactions involved and less sensitive to variations in the quantum yield of the process. We show that BRC can detect attomolar quantities of DNA (10(-18) mol), and that the useful dynamic range is five orders of magnitude. Sensitivity is not constrained by detector performance but rather by background bioluminescence caused by contamination by either PPi or ATP (adenosine triphosphate).

Adenosine Triphosphate↗
PubMed2005

Prediction of missed myocardial infarction among symptomatic outpatients without coronary heart disease.

BACKGROUND: Missed diagnoses of acute myocardial infarction (AMI) in the ambulatory setting can cause patient suffering and malpractice litigation. Multiple algorithms have been developed to detect the presence of coronary heart disease (CHD) or acute coronary ischemia. METHODS: We performed a case-control study of patients with no prior history of CHD presenting to outpatient practices with potential cardiac ischemia. Malpractice claims files were used to identify 18 cases of patients with missed AMIs. For each case, we identified 3 control patients who had office visits for chest pain during the same month and assessed the association of 4 different prediction tools with missed AMI. RESULTS: The 18 cases of missed AMI had a 39% 1-month mortality rate. Cases were more likely than controls to be men (67% vs 26%, P = .001), to be smokers (88% vs 39%, P < .001), and to have low HDL cholesterol (39 mg/dL vs 59 mg/dL, P < .001) and elevated total cholesterol (236 mg/dL vs 213 mg/dL, P = .01). A Framingham risk score predicting a 10-year risk of CHD > or =10% and a positive score using the Goldman risk predictor were associated with an increased risk of missed AMI (odds ratio 5.7, 95% CI 1.8-18.4 for Framingham risk score; odds ratio 7.2, 95% CI 1.4-36.8 for Goldman risk predictor). CONCLUSIONS: Among ambulatory patients with possible cardiac ischemia and no prior CHD, multiple algorithms may be useful for improvement of risk stratification.

Algorithms↗
PubMed2005

The role of cyclooxygenase-2 inhibition in foot and ankle arthrodesis.

Cyclooxygenase-2 (COX-2) inhibitors are an important adjunct in controlling postoperative pain. Concerns exist regarding the use of NSAIDs for postoperative pain management because of the possible deleterious impact on bone healing in patients undergoing hindfoot arthrodesis. Orthopedic surgeons are concerned with: (1) a multimodal approach for postoperative pain control, and (2) bone healing following arthrodesis, fracture repair with rigid internal fixation, and cementless implants. The use of COX-2 inhibitors has been shown to be an important component of a pain control strategy but questions about their effects on bone healing have inhibited their use. This article discusses the laboratory and clinical data available on the use of COX-2 inhibitors on bone healing and their effects on foot and ankle arthrodesis procedures.

Animals↗
PubMed2005

The economic burden of diabetic foot and ankle disorders.

Physicians specializing in the care of patients with lower extremity disorders are acutely aware of the many adverse effects of diabetes mellitus and its secondary complications on all body systems. However, the disease has a devastating socioeconomic impact, as well. An estimated $98 billion in direct and indirect medical costs was spent on diabetes in 1997 in the United States. With a growing older population, cases of diabetes mellitus will certainly increase. The economic impact and clinical effectiveness of patient evaluation, preventive strategies, and treatment options are discussed.

Amputation, Surgical↗
PubMed2005

The peroneal tubercle: description, classification, and relevance to peroneus longus tendon pathology.

BACKGROUND: The size and configuration of the peroneal tubercle has been implicated in the pathogenesis of peroneal tendon tears and tenosynovitis. The purpose of this study was to determine the size and prevalence of the peroneal tubercle and devise a classification scheme according to the structure of the tubercle. METHODS: One hundred and seventeen calcanei were selected from 59 human skeletons in an osteological collection (one calcaneus was missing). Three were excluded because of the poor condition, leaving 114 calcanei. The peroneal tubercle was measured in length, height, and depth and its structure subjectively described as flat, prominent, concave, or tunnel for each specimen when present. RESULTS: This study revealed a peroneal tubercle prevalence of 90.4% (103) in 114 calcanei. The average length, height, and depth of the tubercle were 13.04 mm (range 3.61 mm to 26.66 mm), 9.44 mm (range 3.67 mm to 23.40 mm), and 3.13 mm (range 1 to 10), respectively. The peroneal tubercle was classified structurally as flat in 44 (42.7%), prominent in 30 (29.1%), concave in 28 (27.2%), and tunnel in one (1.0%). CONCLUSION: This data may further help to understand the size and assorted configurations of the peroneal tubercle and how they relate to peroneus longus tendon pathology.

Adult↗