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Biomedical subjects

T K Lee

Publications and source records attributed to T K Lee.

At least 19 recordsLinked to original sources

Clinicopathological significance of homeoprotein Six1 in hepatocellular carcinoma.

Tumour recurrence and metastases of hepatocellular carcinoma (HCC) after hepatectomy are the major obstacles of long-term survival. The present study investigated the clinicopathological significance of a possible metastasis regulator Six1 in HCC patients who were undergone hepatectomy. Seventy-two pairs of RNA and 103 pairs of protein from tumour and adjacent nontumour liver tissues of HCC patients were examined. About 85 and 60% of HCC tumour tissues were found to overexpress Six1 mRNA and protein, respectively, compared with nontumour liver tissues. No Six1 protein was detected in HCC nontumour liver tissues and normal liver tissues. Increased Six1 protein expression in HCC patients was significantly correlated with pathologic tumour-node-metastasis (pTNM) stage (P=0.002), venous infiltration (P=0.004) and poor overall survival (P=0.0423). We concluded that Six1 is frequently overexpressed in HCC patients and elevated Six1 protein in HCC patients may be an indication of advanced stage and poor overall survival after hepatectomy.

Adult↗

Supersolid phase in spin dimer XXZ systems under a magnetic field.

Using the quantum Monte Carlo method, we study, under external magnetic fields, the ground state phase diagram of the two-dimensional spin S=1/2 dimer model with an anisotropic intraplane antiferromagnetic coupling. With the anisotropy 4 greater/approximately Delta greater/approximately 3, a supersolid phase characterized by a nonuniform Bose condensate density that breaks translational symmetry is found. The rich phase diagram also contains a checkerboard solid, an antiferromagnet in the z axis, and a superfluid phase formed by S(z)= +1 spin triplets which has a finite staggered magnetization in the in-plane direction. As we show, the model can be realized as a consequence of including the next nearest neighbor coupling among dimers and our results suggest that spin dimer systems may be an ideal model system to study the supersolid phase.

Journal Article↗

PIN1 expression contributes to hepatic carcinogenesis.

The phospho-Ser/Thr-Pro specific prolyl-isomerase PIN1 is over-expressed in more than 50% of hepatocellular carcinomas (HCCs). To investigate its potential oncogenicity, we over-expressed PIN1 in a non-transformed human liver cell line MIHA. This resulted in up-regulation of beta-catenin and cyclin D1, leading to anchorage-independent growth in soft agar and tumorigenicity in nude mice. To further validate the role of PIN1 in hepatocarcinogenesis, PIN was suppressed by RNA interference (siRNA) in the HCC cell line PLC/PRF/5. siRNA-PIN1 transfection of PLC/PRF/5 cells led to repression of PIN1 expression, resulting in decreased levels of beta-catenin and cyclin D1. siRNA-PIN1 transfectants showed lower cell proliferation rates, reduced colony formation, and retarded cell cycle progression, with an increase in cells residing in G0/G1. Furthermore, soft agar colony formation was depressed, and tumorigenicity in nude mice was abrogated. These findings implicate PIN1 expression as an important step in hepatic carcinogenesis.

Animals↗

Right precordial leads and lead aVR at exercise electrocardiography: does it change test results?

BACKGROUND: A recent study on exercise testing (ET) suggested that ST-segment changes in the right precordial leads (RPL) may increase its sensitivity substantially. However, this study looked at a highly selected population of patients who all underwent thallium-201 scintigraphy and coronary angiography. The present study evaluated the clinical utility of ST-segment changes in the RPL and lead aVR in an unselected population of patients undergoing ET. METHODS: A total of 906 consecutive patients who received ET were included in the study. ET was done using the Bruce Protocol with a 12-lead electrocardiogram (ECG) substituting V(4)R and V(6)R for V(1) and V(6). Leads V(1) and V(6) were selected for omission as these two leads hardly ever manifest changes in isolation. Substituting two leads would obviate the need for a more complex recording system, thus improving clinical utility. RESULTS: On the basis of horizontal/downsloping ST-segment depression (STD) of 1.0 mm or more (the usually accepted criterion for a positive ET), 159 (17.5%) patients had a positive ET. In those patients with a negative ET (545 patients), 4 patients (0.7%) manifested STD and 5 patients (0.9%) manifested ST-segment elevation (STE) in leads V(4)R and/or V(6)R, respectively. Of note, 44.7% of the positive ET group had STE in lead aVR. CONCLUSION: The use of ST-segment changes in RPL during exercise stress testing does not appreciably change the test results of a standard ET. If one was to consider an additional marker, STE in aVR may be more useful, as it shows a stronger correlation with positive tests and does not require the recording of additional leads.

Electrocardiography↗

Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival.

Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small-for-size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small-for-size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat-derived hormone adiponectin (anti-steatosis) plus immunomodulator FTY720 (anti-inflammatory) in a rat liver transplantation model using small-for-size fatty liver grafts, and investigated the underlying protective mechanism such as anti-steatosis, intra-graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7-day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7-day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra-graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat-derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small-for-size fatty liver graft injury.

Adiponectin↗

Rapamycin attenuates liver graft injury in cirrhotic recipient--the significance of down-regulation of Rho-ROCK-VEGF pathway.

To investigate whether rapamycin could attenuate hepatic I/R injury in a cirrhotic rat liver transplantation model, we applied a rat orthotopic liver transplantation model using 100% or 50% of liver grafts and cirrhotic recipients. Rapamycin was given (0.2 mg/kg, i.v.) at 30 min before graft harvesting in the donor and 24 h before operation, 30 min before total hepatectomy and immediately after reperfusion in the recipient. Rapamycin significantly improved small-for-size graft survival from 8.3% (1/12) to 66.7% (8/12) (p = 0.027). It also increased 7-day survival rates of whole grafts (58.3%[7/12] vs. 83.3%[10/12], p = 0.371). Activation of hepatic stellate cells was mainly found in small-for-size grafts during the first 7 days after liver transplantation. Rapamycin suppressed expression of smooth muscle actin, which is a marker of hepatic stellate cell activation, especially in small-for-size grafts. Intragraft protein expression and mRNA levels of vascular endothelial growth factor (VEGF) were down-regulated by rapamycin at 48 h both in whole and small-for-size grafts. Consistently, mRNA levels and protein expression of Rho and ROCK I were decreased by rapamycin during the 48 h after liver transplantation. In conclusion, rapamycin attenuated graft injury in a cirrhotic rat liver transplantation model by suppression of hepatic stellate cell activation, related to down-regulation of Rho-ROCK-VEGF pathway.

Actins↗

Drought-inducible-but ABA-independent-thaumatin-like protein from carrot (Daucus carota L.).

Drought treatment induces the accumulation of dcTLP, which is similar in structure to the thaumatin-like proteins (TLPs) found in the embryogenic calli, seedlings, and mature plants of carrot (Daucus carota). We isolated a full-length dcTLP cDNA clone from carrot and characterized the 5' upstream sequences. The coding region of dcTLP consisted of 645 nucleotides; the theoretical pI value was 4.9, and its molecular weight was approximately 22 kDa. The production of dcTLP transcripts in the seedlings increased dramatically with dehydration treatment but was not affected by abscisic acid (ABA), salicylic acid, or jasmonic acid. The expression patterns of dcTLP mRNA at different developmental stages and in response to a variety of signal molecules was analyzed using reverse transcriptase-PCR and promoter analysis with fused genes of 0.5-kb 5' upstream sequences in which beta-glucuronidase (GUS) reporter genes (gus) were established. The induction of dcTLP was found to be highly specific to drought stress in the embryogenic calli, seedlings, and mature plants. Our results suggest that this new isoform of TLP that has been isolated from carrot is a drought-specific, ABA-independent, non-organ-specific, and non-developmental-stage-specific protein.

Amino Acid Sequence↗

Generalizability and persistence of a multifaceted intervention for improving quality of care for rural patients with type 2 diabetes.

OBJECTIVE: Most quality improvement efforts for type 2 diabetes have neglected cardiovascular risk factors and are limited by a lack of information about generalizability across settings or persistence of effect over time. RESEARCH DESIGN AND METHODS: We previously reported 6-month results of a controlled study of an intervention that improved cardiovascular risk factors for rural patients with type 2 diabetes. We subsequently provided the identical intervention to the control region after the main study was completed. The primary outcome was 10% improvement in systolic blood pressure, total cholesterol, or HbA(1c). We compared the previously reported 6-month effect of the original intervention with the effect of the crossed-over intervention to the former control region and remeasured outcomes in the original intervention region 12 months later. RESULTS: Our analysis included 200 original intervention and 181 crossed-over intervention subjects. The age of the population was 62.4 +/- 12.4 years (mean +/- SD), and 54.3% were women. A similar proportion of patients in the crossed-over intervention group achieved improvement in the primary composite outcome compared with the original intervention group (38 vs. 44%, respectively; P = 0.29). In adjusted analyses, we observed less improvement in blood pressure (adjusted odds ratio 0.40 [95% CI 0.17-0.75]) but greater improvements in total cholesterol (1.86 [0.93-3.7]) with the crossed-over intervention compared with the original intervention. We observed sustained improvements in total cholesterol and HbA(1c) levels in the original intervention group, whereas previous large gains in control of blood pressure diminished over time. CONCLUSIONS: We found that our intervention was generalizable across settings, and its effect persisted over time. Nevertheless, without ongoing intervention or reinforcement, we noted some loss of the original benefits that had accrued. Future translational work should incorporate interventions such as ours into ongoing systems of rural care.

Aged↗

Enhancement of pairing correlation by t' in the two-dimensional extended t-J model.

We investigate the effects of the next-nearest-neighbor (t') and the third-nearest-neighbor (t") hopping terms on superconductivity correlation in the 2D hole-doped extended t-J model based on the variational Monte Carlo, mean-field calculation and exact diagonalization method. Despite the diversity of the methods employed, the results all point to a consistent conclusion: While the d-wave superconductivity correlation is slightly suppressed by t' and t" in underdoped regions, it is greatly enhanced in the optimal and overdoped regions. The optimal Tc is a result of the balance of these two opposite trends.

Journal Article↗

Underuse of aspirin in type 2 diabetes mellitus: prevalence and correlates of therapy in rural Canada.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) have a markedly increased risk of cardiovascular morbidity and mortality. Guidelines of both the American and Canadian Diabetes Associations recommend the use of aspirin as antiplatelet therapy for all adults with type 2 DM. OBJECTIVES: The aims of this study were to assess the rate of adherence to guidelines for aspirin use in DM patients in rural Canadian communities and to describe the independent correlates of aspirin use in this population. METHODS: We collected information from a cohort of patients with type 2 DM living in 2 rural regions of northern Alberta, Canada, at the time of their enrollment in a multidisciplinary outreach program designed to improve their quality of care. Our primary outcome was self-reported use of antiplatelet therapy (aspirin or others). We use multivariate logistic regression analyses to examine the independent association between sociodemographic and clinical characteristics and self-reported use of antiplatelet agents. RESULTS: Among 342 patients included in the study (who were typical of rural Canadian patients with type 2 DM), the mean age was 62.9 years; 149 (44%) were men, 84 (25%) were of indigenous origin, and the median time since diagnosis of DM was 8 years. Despite guideline recommendations, only 23% of the cohort (78 patients) were regularly taking aspirin alone or in combination with a thienopyridine (n = 74 and n = 2, respectively) or a thienopyridine alone (n = 2). The results of them ultivariate analyses showed that the only factors independently associated with the use of antiplatelet therapy were symptomatic coronary artery disease (adjusted odds ratio [AOR], 3.1; 95% CI, 1.1-8.7; P=0.033 ), older age (AOR, 2.0 per 10-year interval; 95% CI, 1.7-2.2; P<0.001 ); and male sex (AOR, 1.9; 95% CI, 1.1-3.5; P=0.026 ). CONCLUSIONS: Aspirin is a safe, inexpensive, and readily available therapy that is effective for preventing cardiovascular disease, and patients with type 2 DM are particularly likely to benefit from such preventive therapy. However, we found significant underuse of aspirin therapy among our study population. Aspirin should be included and better promoted as a factor in high-quality, evidence-based DM management.

Adult↗

Treatment gaps for hypertension management in rural Canadian patients with type 2 diabetes mellitus.

BACKGROUND: There were a reported 2.2 million Canadians living with diabetes mellitus (DM) in 2002, of whom 1.98 million (90.0%) had type 2 DM. In addition, there are approximately 60,000 new cases of type 2 DM diagnosed in Canada each year. However, the research shows that evidence and guidelines for management of hypertension in DM are not always translated into clinical practice. In rural areas, factors affecting implementation of recommendations and/or guidelines are less well understood, although some studies suggest that urban practices provide higher quality of care overall than rural areas. OBJECTIVE: The goal of this study was to describe the patterns of medication use for hypertension for patients with type 2 DM in rural northern Alberta, Canada. We also tried to identify treatment gaps and opportunities for prescribing antihypertensives relative to the Canadian Diabetes Association's 1998 Clinical Practice Guidelines for the Management of Diabetes in Canada and the Canadian Hypertension Society Recommendations Working Group's 2003 Canadian Recommendations for the Management of Hypertension: Therapy. METHODS: This study was conducted at the Institute of Health Economics and the University of Alberta (Edmonton, Alberta, Canada). We collected information from a cohort of patients aged >or =20 years with type 2 DM living in 2 adjacent rural regions of northern Alberta, Canada, at the time of enrollment in a diabetes care quality-improvement program as part of the Diabetes Outreach Van Enhancement (DOVE) study. Treatment gaps were determined by comparing antihypertensive pharmacotherapy with a blood pressure (BP) target of < or =130/< or =85 mm Hg. We used multivariate regression analyses to determine the associations between sociodemographic and clinical characteristics and treatment gaps. RESULTS: A total of 392 patients (229 women, 164 men; mean [SD] age, 62.3 [12.5] years) with type 2 DM were included in this analysis. Patients had a mean (SD) duration of diabetes of 8.3 (8.5) years. A total of 75.8% (297/392) of the study population had hypertension, and most (236/392[60.2%]) were receiving some pharmacotherapy. Treatment gaps were present; 42.7% (n = 67) of patients not receiving pharmacotherapy for hypertension were above the established BP targets. For patients receiving monotherapy, 70% were not at BP targets. For patients receiving dual, triple, and > or =4 medications, 65%, 66%, and 46%, respectively, were not at BP targets. After controlling for systolic blood pressure, male sex (adjusted odds ratio [aOR], 2.17; 95% CI, 1.17-4.03), older age (aOR, 1.80 per decade; 95% CI, 1.51-2.09), lower self-reported physical health (aOR, 0.68; 95% CI, 0.41-0.96), higher body mass index (aOR, 1.05; 95% CI, 1.01-1.10), and past/current smoking (aOR, 1.95; 95% CI, 1.01-3.76) were all significantly associated with a lack of treatment for hypertension. CONCLUSIONS: Treatment maps in the management of hypertension exist in these rural Canadian patients with type 2 DM. Cardiovascular risk may be underestimated in these patients, particularly among younger patients and women, and those with multiple non-DM risk factors. These are patient subgroups that should be targeted as opportunities to improve hypertension management at the population level.

Adult↗

Improvements in patient-reported outcomes associated with an intervention to enhance quality of care for rural patients with type 2 diabetes: results of a controlled trial.

OBJECTIVE: The aim of this study was to examine patient-reported outcomes in a controlled trial of a multifaceted provider-level intervention to improve quality of care for rural patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a before/after intervention study with concurrent controls in two rural regions in Alberta, Canada. The intervention consisted of six monthly visits by a multidisciplinary health care team and was primarily directed at primary care providers. Clinical and patient-reported outcomes were assessed after 6 months. Patient-reported outcomes included changes in health-related quality of life (Health Utilities Index Mark 3 [HUI3]), satisfaction with care, lifestyle (Diabetes Lifestyle Form), and adherence to self-care activities. Analysis of covariance was used to assess differences over time between the control and intervention regions. RESULTS: A total of 200 intervention and 172 control subjects were included in this analysis. After adjusting for important clinical and demographic differences, a statistically significant and clinically important improvement in the overall HUI3 score was seen at the 6-month follow-up in the intervention region (0.06 [95% CI 0.02-0.10]) compared with the control region (0.01 [-0.04 to 0.04]) (P = 0.03 for the difference between groups). Satisfaction with general medical care (P < 0.001 between groups) and diabetes care (P < 0.001 between groups) increased among patients in the intervention region compared with the control region. Self-efficacy, attitudes, and beliefs about diabetes control all increased in the intervention region when compared with the control region, but adherence to self-care activities did not. CONCLUSIONS: A provider-level intervention directed at improving quality of clinical care for patients with type 2 diabetes also had a favorable impact on overall health-related quality of life, satisfaction with care, and other humanistic outcomes.

Alberta↗

Cytokine profiles in patients receiving wide-field + prostate boost radiotherapy (xRT) for adenocarcinoma of the prostate.

As a result of the association between ionizing irradiation and the induction of inflammatory and fibrogenic cytokines, circulating levels of IL-1alpha, macrophage colony stimulating factor (M-CSF) and TGFbeta were measured in a group of 37 patients who presented with well-defined adenocarcinoma of the prostate and were treated with wide-field pelvic (WFP) + prostate boost (PB) radiotherapy (xRT) according to RTOG protocols 94-08 and 94-13. First and foremost, patients with prostate cancer (PC) were found to have a significantly (p<0.05) elevated plasma level of the three cytokines prior to treatment. Moreover, during WFP + PB xRT, these circulating cytokine levels were further elevated, the elevation occurring in the form of cyclic waves; the concurrent waves of elevated IL-1alpha and M-CSF preceding that of TGFbeta. In addition to providing support for the existence of a humoral response to xRT in patients receiving WFP + PB xRT, the data demonstrated a significant correlation between the integral radiation dose (ID) and the temporal expression and magnitude of plasma IL-1alpha, M-CSF and TGFbeta levels in patients that had received 1-5 fractions (1.8-9Gy) of WFP + PB xRT. Thereafter, the appearance of elevated waves of cytokine expression in the patient's plasma continued independent of additional fractions of WFP + PB xRT.

Adenocarcinoma↗

Low-energy spectra in t-J-type models at low doping levels.

Based on a variational approach, we propose that there are two kinds of low-energy states in the t-J-type models at low doping. In a quasiparticle state an unpaired spin bound to a hole with a well-defined momentum can be excited with spin waves. The resulting state shows a suppression of antiferromagnetic order around the hole with the profile of a spin bag. These spin-bag states with spin and charge or hole separated form a continuum of low-energy excitations. Very different properties predicted by these two kinds of states explain a number of anomalous results observed in the exact diagonalization studies on small clusters up to 32 sites.

Journal Article↗

Theory for slightly doped antiferromagnetic mott insulators.

New trial wave functions, constructed explicitly from the unique Mott insulating state with antiferromagnetic order, are proposed to describe the ground state of a Mott insulator slightly doped with holes or electrons. A rigid band is observed as charged quasiparticles with well-defined momenta being realized in these states. These states have much less superconducting correlations than previously studied ones. Small Fermi patches obtained are consistent with recent experiments on high T(c) cuprates doped lightly with holes or electrons.

Journal Article↗

Misidentification of Aeromonas veronii biovar sobria as Vibrio alginolyticus by the Vitek system.

AIMS: To find the cause of misidentification of aeromonads when using the Vitek system. METHODS AND RESULTS: Two Aeromonas veronii biovar sobria isolates were misidentified as Vibrio alginolyticus by the Vitek system. Both strains' identification was confirmed by biochemical testing, API 20E/20NE kits and/or 16S RFLP analysis. Thirty-one known Aeromonas species were tested by the Vitek system using 0.45 and 0.85% saline in the suspension medium. It was not clear whether low salinity causes misidentification of Aeromonas species more frequently. CONCLUSIONS: The specified reaction time may be inappropriately short for some critical biochemical tests of some strains. An ingenious reading strategy regarding incubation time is necessary to improve identification of Aeromonas species by the Vitek system. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report of misidentification of A. veronii biovar sobria as V. alginolyticus in the Vitek system.

Aeromonas↗

Controlled trial of a multifaceted intervention for improving quality of care for rural patients with type 2 diabetes.

OBJECTIVE: Despite good evidence and clinical practice guidelines, studies document that treatment of type 2 diabetes is less than optimal. Lack of resources or limited access may put patients in rural communities at particular risk for suboptimal care. RESEARCH DESIGN AND METHODS: We conducted a prospective, before/after study with concurrent controls to assess the effectiveness of a multidisciplinary diabetes outreach service (intervention) for improving the quality of care for rural patients with type 2 diabetes. Our intervention consisted of six monthly visits by a traveling team of specialist physicians, nurses, dieticians, and a pharmacist. The core of this service was specialist-to-rural primary care physician academic group detailing. Two comparable regions in Northern Alberta were randomly allocated to control or intervention. Data were collected before and 6 months after intervention in a representative volunteer sample. The primary outcome was a 10% improvement in any one of the following: blood pressure, total cholesterol, or HbA(1c). RESULTS: Our analysis included 200 intervention and 179 control subjects; 14 subjects were at all three primary outcome targets at baseline. The intervention was associated with a trend toward improvement in primary outcome at 6 months (44% intervention vs. 37% control; odds ratio 1.32, 95% CI 0.87-1.99). The intervention was associated with a significant improvement in blood pressure (42% intervention vs. 25% control, P = 0.004); however, there were only small, nonsignificant changes in cholesterol or HbA(1c). The intervention was associated with a significant increase in satisfaction with diabetes care. Multivariate adjustment for baseline differences between intervention and control subjects did not affect any of the main results. CONCLUSIONS: A diabetes outreach service has the potential to improve the quality of diabetes care for rural patients. Future studies need to involve longer timelines and larger sample sizes.

Aged↗