Search PubMed⌕ Search

Biomedical subjects

T W Lee

Publications and source records attributed to T W Lee.

At least 55 records · Page 3Linked to original sources

Human CC chemokine I-309, structural consequences of the additional disulfide bond.

I-309 is a member of the CC subclass of chemokines and is one of only three human chemokines known to contain an additional, third disulfide bond. The three-dimensional solution structure of I-309 was determined by (1)H nuclear magnetic resonance spectroscopy and dynamic simulated annealing. The structure of I-309, which remains monomeric at high concentrations, was determined on the basis of 978 experimental restraints. The N-terminal region of I-309 was disordered, as has been previously observed for the CC chemokine eotaxin but not others such as MCP-1 and RANTES. This was followed in I-309 by a well-ordered region between residues 13 and 69 that consisted of a 3(10)-helix, a triple-stranded antiparallel beta-sheet, and finally a C-terminal alpha-helix. Root-mean-square deviations of 0.61 and 1.16 were observed for the backbone and heavy atoms, respectively. A comparison of I-309 to eotaxin and HCC-2 revealed a significant structural change in the C-terminal region of the protein. The alpha-helix normally present in chemokines was terminated early and was followed by a short section of extended strand. These changes were a direct result of the additional disulfide bond present in this protein. An examination of the I-309 structure will aid in an understanding of the specificity of this protein with its receptor, CCR8.

Amino Acid Sequence↗

The effect of pH on beta(2) adrenoceptor function. Evidence for protonation-dependent activation.

The transition of rhodopsin from the inactive to the active state is associated with proton uptake at Glu(134) (1), and recent mutagenesis studies suggest that protonation of the homologous amino acid in the alpha(1B) adrenergic receptor (Asp(142)) may be involved in its mechanism of activation (2). To further explore the role of protonation in G protein-coupled receptor activation, we examined the effects of pH on the rate of ligand-induced conformational change and on receptor-mediated G protein activation for the beta(2) adrenergic receptor (beta(2)AR). The rate of agonist-induced change in the fluorescence of NBD-labeled, purified beta(2)AR was 2-fold greater at pH 6.5 than at pH 8, even though agonist affinity was lower at pH 6.5. This biophysical analysis was corroborated by functional studies; basal (agonist-independent) activation of Galpha(s) by the beta(2)AR was greater at pH 6.5 compared with pH 8.0. Taken together, these results provide evidence that protonation increases basal activity by destabilizing the inactive state of the receptor. In addition, we found that the pH sensitivity of beta(2)AR activation is not abrogated by mutation of Asp(130), which is homologous to the highly conserved acidic amino acids that link protonation to activation of rhodopsin (Glu(134)) and the alpha(1B) adrenergic receptor (Asp(142)).

Animals↗

VATS lobectomy reduces cytokine responses compared with conventional surgery.

BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy for early lung cancer has been shown to be technically feasible. Comparative studies on laparoscopic versus open procedures indicate that laparoscopy may reduce inflammatory reactions as reflected by the lesser release of cytokines. We investigated the cytokine responses following VATS and conventional lobectomy for clinical stage I lung cancer. METHODS: Thirty-six patients with clinical stage I nonsmall cell lung cancer were studied. 18 patients underwent VATS lobectomy and the other 18 by conventional thoracotomy. There were no differences between the two groups with respect to age, gender, pulmonary function, smoking history, comorbidity, tumor size, and pathology. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-8, and an antiinflammatory cytokine IL-10 were measured before surgery, at the end of the procedure, and 4, 8, 24, and 48 hours thereafter in all patients. RESULTS: There was no mortality or major complication in either group. Analgesic requirement was significantly less in the VATS group. Although the release of TNF-alpha and IL-1beta were minimal after surgery in both groups, the levels of IL-6, IL-8, and IL-10 were elevated. IL-6 and IL-8 levels were significantly lower in the VATS group at the end of surgery than in the open group. In addition, reduced release of IL-10 was also observed in the VATS group shortly after surgery. CONCLUSIONS: VATS lobectomy is associated with reduced postoperative release of both proinflammatory and antiinflammatory cytokines compared with the open approach. The clinical significance of these findings remains to be fully elucidated.

Aged↗

'Needlescopic' video-assisted thoracic surgery for palmar hyperhidrosis.

OBJECTIVE: The video-assisted thoracic surgery (VATS) approach for thoracodorsal sympathectomy has been well accepted. We report the use of ultra-fine thoracoscopic equipment for this procedure, based on the experience from two centers in Asia. MATERIALS AND METHODS: Thirty-eight patients with palmar hyperhidrosis underwent bilateral VATS thoracodorsal sympathectomy using 2-mm instruments exclusively. General anesthesia with selective one lung ventilation was used. Carbon dioxide insufflation was used when lung collapse was found to be inadequate. In 11 patients, the sympathetic chain was excised (T2-T3 for palmar hyperhidrosis alone, extending to T4 for axillary hyperhidrosis), and in 27 patients, the chain was cauterized. The choice of procedure reflects the surgeon's preference. No chest drains were left after the procedure and no stitching of the wound was necessary. RESULTS: There was no mortality or major complications. A small pneumothorax was found in the postoperative chest X-ray in three patients. They all resolved without further intervention. Twenty-seven patients were discharged on the same day of admission, and 11 patients were discharged on postoperative day one. After an average follow-up of 16 months (range 5-28), there has been no recurrence of symptoms. Compensatory truncal hyperhidrosis was encountered in two patients, but the symptoms were not severe enough to interfere with lifestyle, and this required no further treatment. CONCLUSION: Thoracodorsal sympathectomy using 2-mm instruments is technically feasible and is associated with an excellent clinical outcome. Limitations of the equipment, however, exist (narrow field of vision, lower resolution and difficulty in maintaining fine control), and we are currently restricting its use to relatively simple procedures.

Adult↗

Can CT scanning be used to select patients with unilateral primary spontaneous pneumothorax for bilateral surgery?

STUDY OBJECTIVES: Despite advances in the surgical treatment of spontaneous pneumothorax, the timing of surgical intervention continues to be a subject of controversy. We test the hypothesis that CT scanning can help to predict the probability of the occurrence of primary spontaneous pneumothorax (PSP) by detecting lung bullae. DESIGN: Prospective, longitudinal cohort study. PATIENTS AND METHODS: Between May 1994 to March 1995, 28 consecutive patients (23 men; age range, 18 to 47 years; mean, 29 years) with unilateral PSP who were to undergo video-assisted thoracic surgery (VATS) received preoperative CT of the thorax. CT scans were interpreted by one radiologist blinded to the clinical data for the presence of bullae in both lungs. All patients were followed-up in our outpatient clinic for an average of 59.0 months (range, 54 to 64 months). RESULTS: Eighty-eight percent of the blebs or bullae identified intraoperatively were demonstrated on preoperative CT scans. CT scans also showed the presence of lung blebs or bullae in the contralateral lung in 15 patients (53.6%). During the follow-up period, 4 of these 15 patients (26.7%) with contralateral blebs developed PSP in the untreated lung; none of the patients who did not have contralateral blebs (n = 13) developed PSP (p = 0.04 [chi(2) analysis]). CONCLUSIONS: The detection of lung bullae by CT scanning in the contralateral lung following unilateral PSP is associated with a higher rate of subsequent occurrence of pneumothorax in that lung. Thus, CT scanning can be used to predict the risk of occurrence of this condition, allowing preemptive surgical intervention in selected patients.

Adolescent↗

Removing electroencephalographic artifacts by blind source separation.

Eye movements, eye blinks, cardiac signals, muscle noise, and line noise present serious problems for electroencephalographic (EEG) interpretation and analysis when rejecting contaminated EEG segments results in an unacceptable data loss. Many methods have been proposed to remove artifacts from EEG recordings, especially those arising from eye movements and blinks. Often regression in the time or frequency domain is performed on parallel EEG and electrooculographic (EOG) recordings to derive parameters characterizing the appearance and spread of EOG artifacts in the EEG channels. Because EEG and ocular activity mix bidirectionally, regressing out eye artifacts inevitably involves subtracting relevant EEG signals from each record as well. Regression methods become even more problematic when a good regressing channel is not available for each artifact source, as in the case of muscle artifacts. Use of principal component analysis (PCA) has been proposed to remove eye artifacts from multichannel EEG. However, PCA cannot completely separate eye artifacts from brain signals, especially when they have comparable amplitudes. Here, we propose a new and generally applicable method for removing a wide variety of artifacts from EEG records based on blind source separation by independent component analysis (ICA). Our results on EEG data collected from normal and autistic subjects show that ICA can effectively detect, separate, and remove contamination from a wide variety of artifactual sources in EEG records with results comparing favorably with those obtained using regression and PCA methods. ICA can also be used to analyze blink-related brain activity.

Artifacts↗

Management of massive hemoptysis: a single institution experience.

BACKGROUND: Massive hemoptysis is a life threatening condition. Several therapeutic strategies have been applied in the clinical setting, with variable results. We reviewed our recent experience on this subject. MATERIAL AND METHODS: In a 5-year period, fifty-four patients (41 males, mean age 57.9 years) were treated for massive hemoptysis in our unit. The underlying pathology included bronchiectasis (n=31), active tuberculosis (n=9), pneumoconiosis (n=3), lung cancer (n=2) and pulmonary angiodysplasia (n=1). These patients often present with continuous bleeding with large volume of hemoptysis, or with recurrent episodes of bleeding. Bronchoscopic assessment and interventions were performed upon admission in all patients. Surgery was considered if the patient had acceptable pulmonary reserve and a bleeding source was clearly identified. If the patient was not considered fit for surgery, bronchial artery embolization was attempted. RESULTS: Hemoptysis ceased with conservative management in 7 patients (13%) only. Twenty seven (50%) patients received surgical resection. The procedures included lobectomy (n=21), bilobectomy (n=4) and pneumonectomy (n=2). The in-hospital mortality after surgery was 15%. Postoperative morbidity occurred in 8 patients, including prolonged ventilatory support, bronchopleural fistulae, empyema and myocardial infarction. Twenty-one patients not suitable for surgery were treated with bronchial artery embolisation, which was successful in 17 patients without any complications. CONCLUSION: The clinical outcome for massive hemoptysis reflects the generalized nature of a destructive disease process involving both lungs and a limited respiratory reserve. Surgery is associated with high risk of morbidity and mortality, and should be performed only in selected patients. Meanwhile, aggressive conservative therapy including bronchial artery embolization should be pursued.

Adolescent↗

Restricting the mobility of Gs alpha: impact on receptor and effector coupling.

The alpha-subunit of the stimulatory G protein, Gs, has been shown to dissociate from the plasma membrane into the cytosol following activation by G protein-coupled receptors (GPCR) in some experimental systems. This dissociation may involve depalmitoylation of an amino-terminal cysteine residue. However, the functional significance of this dissociation is not known. To investigate the functional consequence of Gs alpha dissociation, we constructed a membrane-tethered Gs alpha (tetGs alpha), expressed it in Sf9 insect cells, and examined its ability to couple with the beta(2) adrenoceptor and to activate adenylyl cyclase. Compared to wild-type Gs alpha, tetGs alpha coupled much more efficiently to the beta 2 adrenoceptor and the D1 dopamine receptor as determined by agonist-stimulated GTP gamma S binding and GTPase activity. The high coupling efficiency was abolished when Gs )alpha was proteolytically cleaved from the membrane tether. The membrane tether did not prevent the coupling of tetGS alpha to adenylyl cyclase. These results demonstrate that regulating the mobility of Gs alpha relative to the plasma membrane, through fatty acylation or perhaps interactions with cytoskeletal proteins, could have a significant impact on receptor-G protein coupling. Furthermore, by enabling the use of more direct measures of receptor-G protein coupling (GTPase activity, GTP gamma S binding), tetGS alpha can facilitate the study for receptor-G protein interactions.

Adenylyl Cyclases↗

Independent component analysis using an extended infomax algorithm for mixed subgaussian and supergaussian sources.

An extension of the infomax algorithm of Bell and Sejnowski (1995) is presented that is able blindly to separate mixed signals with sub- and supergaussian source distributions. This was achieved by using a simple type of learning rule first derived by Girolami (1997) by choosing negentropy as a projection pursuit index. Parameterized probability distributions that have sub- and supergaussian regimes were used to derive a general learning rule that preserves the simple architecture proposed by Bell and Sejnowski (1995), is optimized using the natural gradient by Amari (1998), and uses the stability analysis of Cardoso and Laheld (1996) to switch between sub- and supergaussian regimes. We demonstrate that the extended infomax algorithm is able to separate 20 sources with a variety of source distributions easily. Applied to high-dimensional data from electroencephalographic recordings, it is effective at separating artifacts such as eye blinks and line noise from weaker electrical signals that arise from sources in the brain.

Algorithms↗

Thoracoscopic surgery for pulmonary tuberculosis.

Tuberculosis historically was a major impetus for the development of thoracic surgery, and it remains a serious health problem of global proportion. Thoracoscopy was first introduced at the turn of this century for closed chest adhesiolysis as an adjunct to collapse therapy for treatment of tuberculosis. This indication became obsolete with the discovery of streptomycin during the 1940s; and for a long time since then thoracoscopy was used only sporadically for the diagnosis of pleural disease. However, over the last few years, modern video-assisted thoracoscopic surgery (VATS) has provided a new approach to the management of pulmonary tuberculosis. Over the last 5 years we have used VATS for diagnosis or treatment (or both) of 62 patients with pulmonary tuberculosis, including 20 pleural biopsies, 8 decortications, 17 wedge lung resections, 8 drainages of empyema, and 9 lobectomies. There was no surgical mortality, and complications were few. We conclude that VATS provides a safe, effective diagnostic modality (pleural biopsy, wedge resections) and therapeutic modality (decortications, drainage of empyema) for selected patients with pulmonary tuberculosis.

Adolescent↗

Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury.

BACKGROUND: Proinflammatory cytokines play a key role in the inflammatory cascade after cardiopulmonary bypass and may induce cardiac dysfunction. We compared the production of cytokines and the degree of postoperative myocardial injury in patients with multivessel coronary artery disease undergoing coronary artery bypass grafting through median sternotomy with or without cardiopulmonary bypass. METHODS: Forty-four consecutive patients were studied. Patients were selected for off-pump coronary artery bypass grafting whenever complete revascularization was technically feasible. There were no differences between the two groups with respect to age, sex, symptoms, or functional class. Plasma levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured before the operation, at the end of the procedure, and 2, 4, 8, 24, and 48 hours thereafter. Levels of the MB isoenzyme of creatine kinase and cardiac troponin-I were also measured after the operation. RESULTS: The number of grafts was 2+/-0.7 in the off-pump group (n = 18) and 3+/-0.8 in the cardiopulmonary bypass group (n = 26). There were no deaths or major complications in either group. Levels of tumor necrosis factor-alpha were low in both groups. No significant intergroup differences were noted regarding serial IL-6 measurements. However, IL-8 and IL-10 levels after the operation were lower in the off-pump group (IL-8, 4+/-1 versus 38+/-12 pg/mL, p < 0.01; IL-10, 5+/-2 versus 191+/-33 pg/mL, p < 0.001). Whereas postoperative creatine kinase-MB values were similar in the two groups, cardiac troponin-I levels were significantly lower in the off-pump group (8 hours, p < 0.005; 24 hours, p < 0.02, respectively). Moreover, cardiac troponin-I values 24 hours after operation correlated strongly with IL-8 levels (r = 0.61, p < 0.005), indicating that the degree of myocardial injury may be related to IL-8 production. CONCLUSIONS: Compared with conventional coronary artery bypass grafting, coronary revascularization without cardiopulmonary bypass is associated with reduced cytokine responses and less myocardial injury.

Cardiopulmonary Bypass↗

Video-assisted thoracic surgery: a renaissance in surgical therapy.

Within a few years, video-assisted thoracic surgery (VATS) has become the accepted or preferred approach over a wide range of thoracic procedures. The authors review the development of this technique, the basic operative strategies and the current surgical indications. Technical pitfalls and future developments are also discussed.

Humans↗

Video-assisted thoracoscopic thymectomy.

Video-assisted thoracoscopic surgery (VATS) provides a new, alternative approach to thymectomy and has several advantages over the other established techniques. However, even among surgeons using this approach, there are differences in the actual technique. We prefer the right approach using conventional instruments. The rationale behind our technique is discussed.

Humans↗

Can cardioplegia management influence cytokine responses during clinical cardiopulmonary bypass?

BACKGROUND: Cytokines play an important role in the inflammatory response associated with cardiopulmonary bypass (CPB) and may contribute to postoperative complications. Although it has been shown that the production of tumor necrosis factor a (TNF-a) and interleukin (IL)-6 were higher following normothermic CPB than hypothermic CPB, whether different cardioplegic management could influence the release of cytokines remains unknown. METHODS: We compared the blood concentrations of four cytokines (TNF-a, IL-6, IL-8, and IL-10) in two groups of patients undergoing complete revascularization with CPB in the same study period. Seventeen patients received cold crystalloid cardioplegia at a Belgian center (group-CC), while 21 patients received warm blood cardioplegia at a center in Hong Kong (group-WB). Blood samples were collected before and after surgery in each patient. RESULTS: There were no differences between the 2 groups in terms of age, sex ratio, number of grafts, duration of CPB and aortic crossclamping. All patients survived their hospital stay. The levels of TNF-a, IL-6 and IL-8 after surgery were higher in group-CC than in group-WB. However, IL-10 levels were significantly lower at the end of surgery in group-CC than in group-WB. CONCLUSIONS: Our data suggest that the use of warm blood cardioplegia, rather than cold crystalloid cardioplegia, may reduce the inflammatory response to CPB. This observation warrants future randomized investigation to determine its clinical relevance.

Blood↗

A cross-sectional survey of physical activity among middle aged women in Singapore.

OBJECTIVES: To assess the extent to which middle-aged women in Singapore engage in physical activity of a level which would result in long-term health benefits, and to determine the factors associated with this. METHODS: We conducted a cross-sectional survey of women aged between 35 and 60 years residing in Marine Terrace. A standardised questionnaire incorporating a modified Seven-Day Recall Questionnaire was used to record the level and type of physical activity engaged in over the past week. Demographic information and factors promoting or discouraging sports and exercise were also elicited. The total energy expenditure for household, occupational and sports activities of moderate intensity and above was calculated using metabolic equivalents (METs) in kcal/kg/week. RESULTS: Of the 341 respondents, 50.7% reported engaging in at least moderate activity for 30 minutes or more every day during the past week, thus fulfilling the WHO recommendations on physical activity. Housework contributed significantly to the energy expenditure on these activities among our target population. After adjusting for age, body mass index and educational level, we found that housewives without domestic help were most likely to fulfill the WHO recommendations. Housewives or working women with domestic help were the two groups at highest risk of low physical activity. A lack of time was the reason most commonly cited for not engaging in sports or exercise. CONCLUSION: Studies assessing physical activity in relation to disease risk among women should include domestic work in addition to the traditional leisure-time activities. There is a scope for further efforts to improve the level of activity in this population, which could be facilitated by the support of health professionals, employers and family members.

Adult↗