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Biomedical subjects

B Lee

Publications and source records attributed to B Lee.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2006

Lower body negative pressure treadmill exercise is more comfortable and produces similar physiological responses as weighted vest exercise.

Lower body negative pressure (LBNP) treadmill exercise can generate a hypergravity load on the lower body that may improve athlete performance by mechanical and cardiovascular adaptations. This study compared the cardiovascular responses, subjective exertion and discomfort levels produced by LBNP exercise with those generated by a weighted vest (WV). We hypothesized that LBNP exercise is more comfortable than WV exercise at comparable levels of exercise. Nine subjects exercised on a treadmill at nine conditions, at 5.5 mph for 15 minutes, in which they ran in random order to avoid confounding effects: 100 %, 110 %, 120 %, 130 %, and 140 % body weight (BW), the latter four conditions were achieved by either LBNP chamber or WV. Heart rate (HR) and oxygen consumption (.VO(2)) were monitored continuously using ECG and open circuit spirometry. At the end of each test, subjects were asked to give discomfort and exertion scores using a ten-point visual analog scale (10 = maximal discomfort and exertion). For both HR and .VO(2), no significant differences were observed between LBNP and WV. Subjects reported significantly higher discomfort levels when exercising with the WV than with the LBNP at 120 % BW (5.1 +/- 0.55 vs. 3.1 +/- 0.64; p < 0.05), 130 % BW (6.2 +/- 0.42 vs. 2.3 +/- 0.44; p < 0.01) and 140 % BW (6.9 +/- 0.27 vs. 4.7 +/- 0.60; p < 0.01), while maintaining similar exertions at all conditions. Based on these results, LBNP exercise is more comfortable than standard WV exercise, while maintaining similar exertion, HR and .VO(2) values.

Adult↗
PubMed2006

Congenital diaphragmatic hernia associated with duplication of 11q23-qter.

Congenital diaphragmatic hernia (CDH) is a relatively common birth defect with a high mortality. Although little is known about its etiology, there is increasing evidence for a strong genetic contribution. Both numerical and structural chromosomal abnormalities have been described in patients with CDH. Partial trisomy 11q and partial trisomy 22 associated with the common t(11;22) has been reported in several cases of CDH. It has been assumed that the diaphragmatic defect seen in these individuals was primarily due to duplication of material from chromosome 22q11. However, in this report we describe a family with a t(11;12) in which one of two brothers with partial trisomy 11q has a left sided posterolateral CDH. This is the second case of CDH in partial trisomy 11q due to an unbalanced translocation other than t(11;22). Using array-based comparative genomic hybridization and fluorescent in situ hybridization, we mapped the breakpoints in both brothers and their mother who is a balanced translocation carrier. Our results suggest that duplication of one or more genes on a approximately 19 Mb region of 11q23.3-qter predisposes to the development of CDH. These effects may be the primary cause of CDH in individuals t(11;22) or may be additive to effects from the duplication of chromosome 22 material. We also conclude that the partial trisomy 11q syndrome has a variable phenotype and that CDH should be added to the spectrum of anomalies that can be present in this syndrome.

Adult↗
PubMed2006

Identifying outcomes from the nursing outcomes classification as indicators of quality of care in Korea: a modified delphi study.

BACKGROUND: The evaluation of patient outcomes as a measure of quality control of patient care is being adopted in Korean hospitals. Since nursing care contributes to the bulk of patient care, it is important to identify nursing-sensitive patient outcomes, hereafter referred to as 'nursing outcomes', that will be useful in the evaluation of nursing care. OBJECTIVE: This study was conducted to identify nursing outcomes included within the Nursing Outcomes Classification (NOC) that are most sensitive for the evaluation of nursing care in Korean hospitals as well as being observable and measurable. DESIGN: Delphi technique modified for this study was used to gain a consensus from Korean nursing experts. SETTINGS: Participants were recruited from general hospitals in Korea. PARTICIPANTS: Two hundred and thirty nurses working for Quality Improvement (QI) and Continuous Quality Improvement (CQI) programmes were chosen as the nurse experts for this study. METHODS: Three rounds of data collection from all participants was undertaken. In the first data collection, the sensitivity of 260 NOC nursing outcomes (Johnson, et al., 2000. Iowa Outcomes Projects: Nursing Outcomes Classification (NOC). C.V. Mosby, St. Louis) was examined, and more highly nursing sensitive ones were selected. In the second and third data collection phases, nursing outcomes which are most useful for the evaluation of nursing care were selected. RESULTS: Vital Signs Status, Knowledge: Infection Control, Pain Control, Safety Behavior: Fall Prevention, and Infection Status were identified as the five most useful nursing outcomes for the evaluation of nursing care in hospitals. CONCLUSIONS: The nursing outcomes identified highly useful for the evaluation of nursing care in this study can be used effectively for the quality management of nursing care in Korea.

Adult↗
PubMed2006

Modulation of TNFalpha, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors.

Understanding the determinants of the host innate immune response to systemic administration of adenoviral (Ad) vectors is critical for clinical gene therapy. Acute toxicity occurs within minutes to hours after vector administration and is characterized by activation of innate immune responses. Our data indicate that in mice, indicators of vector toxicity include elevations of cytokine levels, liver transaminase levels and thrombocytopenia. To discern potential targets for blunting this host response, we evaluated genetic factors in the host response to systemically administered first-generation Ad vectors (FGV) and helper-dependent Ad vectors (HDV) containing beta-galactosidase expression cassettes. A preliminary screen for modulation of vector-induced thrombocytopenia revealed no role for interferon-gamma, mast cells or perforin. However, vector-induced thrombocytopenia and interleukin 6 (IL-6) expression are less evident in tumor necrosis factor alpha (TNFalpha)-deficient mice. Moreover, we also demonstrated that TNFalpha blockade via antibody or huTNFR:Fc pretreatment attenuates both thrombocytopenia (>40% increase in platelet count) and IL-6 expression (>80% reduction) without affecting interleukin 12 , liver enzymes, hematological indices or vector transduction in a murine model. Our data indicate that the use of HDV, in combination with clinically approved TNFalpha immunomodulation, may represent an approach for improving the therapeutic index of Ad gene therapy for human clinical trials.

Adenoviridae↗
PubMed2006

Endovenous laser treatment for long saphenous vein incompetence.

BACKGROUND: Endovenous laser treatment is a percutaneous technique used for the treatment of long saphenous vein (LSV) incompetence. This paper presents the results of an uncontrolled case series undertaken to assess the feasibility, safety and efficacy of this technique. METHODS: Some 145 incompetent LSVs in 136 patients with saphenofemoral reflux were treated with endovenous laser. The data were evaluated prospectively. Assessment was carried out at 1 week, 3 and 12 months for LSV occlusion and symptomatic relief. RESULTS: Primary procedural success was achieved in 124 (85.5 per cent) of 145 LSVs. Reasons for primary failure included failed cannulation, failure to pass the guidewire and patient discomfort. At 3 months' follow-up, 105 (89.7 per cent) of 117 veins were totally and nine (7.7 per cent) were partially occluded. At 12 months, 63 (76 per cent) of 83 veins were totally and 15 (18 per cent) were partially occluded. At this stage 73 (88 per cent) of 83 patients remained satisfied, but 26 (31 per cent) had residual or recurrent varicosities. Of these, only five required further treatment. Complications included saphenous nerve injury in one patient and superficial skin burns in a second. CONCLUSION: Endovenous laser treatment for LSV reflux is safe and can be carried out under local anaesthesia in an outpatient setting with good patient satisfaction and low complication rates.

Adult↗
PubMed2006

Helper-dependent adenoviral gene therapy mediates long-term correction of the clotting defect in the canine hemophilia A model.

BACKGROUND: Adenoviral vector-mediated gene therapy might have potential for long-term correction of the monogenic disease hemophilia A. OBJECTIVE: In this study, we tested the efficacy of administering a helper-dependent adenoviral vector (HDV) designed for maximal liver-restricted canine factor VIII (cFVIII) expression on three out-bred hemophilia A dogs. METHODS: Three FVIII-deficient animals from the University of North Carolina colony were injected with 1 x 10(12) (Dog A), and 3 x 10(12) (Dog B and C) vp kg(-1) helper-dependent adenoviral vector, and we performed systematic analysis of toxicity, persistence of therapeutic gene expression, and molecular analysis of gene transfer. RESULTS: We observed acute dose-dependent elevation in liver enzymes and thrombocytopenia after injection, although both were transient and resolved within 2 weeks. The whole blood clotting time (WBCT), plasma FVIII concentration, FVIII activity, and activated partial thromboplastin time in all animals improved significantly after treatment, and two animals receiving a higher dose reached near normal WBCT with low-level FVIII activity until terminal sacrifice at 3 months, and 2 years. Importantly, the treated dogs suffered no bleeding events after injection. Moreover, we observed persistent vector-specific DNA and RNA in liver tissue collected from one high-dose animal at days 18 and 79, and could not detect the formation of inhibitory antibodies. CONCLUSION: Although vector-associated toxicity remains an obstacle, a single injection of HDV led to long-term transgene expression and vector persistence in two FVIII-deficient animals with conversion of their severe phenotype to a moderate one.

Adenoviridae↗
PubMed2006

Non-surgical alternatives to invasive procedures in mice.

We have developed and validated catheterization protocols in mice that allow for simultaneous infusion and sampling. A sampling catheter was inserted in the lateral vein of the tail, while the animals were infused either intravenously or intragastrically through a second catheter placed in the contralateral lateral vein or via an intragastric catheter, respectively. The applicability of these methods of infusion and blood sampling were validated by conducting urea kinetics utilizing stable isotopes. These non-surgical procedures are non-invasive, inexpensive, fast to perform and animals do not require a recovery period before their use.

Animals↗
PubMed2005

The effect of pravastatin on intima media thickness of the carotid artery in patients with normal cholesterol.

OBJECTIVE: Carotid intima media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. Statins have been found to reduce carotid IMT in patients with hypercholesterolaemia. The aim of this study was to investigate if pravastatin is effective in reducing IMT in normocholesterolaemic patients with carotid artery disease. METHODS: Patients with carotid artery stenosis and normal cholesterol levels who were not on a statin, were recruited. Patients were randomised to receive pravastatin or placebo daily. Serum concentration of cholesterol and IMT of common carotid arteries were measured before randomisation and at 3 monthly intervals thereafter, for 9 months. IMT was analysed to give the mean of a standardised 2 cm of the common carotid artery (CCA). Results are expressed as median (IQR) and comparison made using the Wilcoxon signed ranks test. RESULTS: Fifty-four patients were examined. Twenty-eight patients were randomised to active treatment. There was no difference in demographic details and co-morbid states between the two groups. A significant reduction in cholesterol concentration was observed from 3 months in patients randomised to the pravastatin group [5.14(4.72-5.88) vs. 4.11(3.44-5.33), p < 0.05], while there was also a significant decrease in combined IMT form 6 months [1.53(1.36-1.87) vs. 1.41 (1.33-1.78), p < 0.05]. CONCLUSIONS: The results demonstrate that pravastatin reduces intima media thickness of the common carotid artery in normocholesterolaemic patients with moderate carotid stenosis.

Aged↗
PubMed2005

Multivariate analysis of the effectiveness of using antibody induction therapy according to the degree of HLA mismatches.

OBJECTIVE: HLA mismatches have a strong impact on acute rejection and renal allograft survival. The objective of this study was to evaluate the effectiveness of antibody induction according to the degree of HLA mismatches. METHODS: Of 20,429 deceased donor (DD) transplantations and 12,859 living donor (LD) transplantations reported to the United Network for Organ Sharing (UNOS) between 1999 and 2001, 51% of DD and 45% of LD transplant recipients received induction therapy. Propensity scores (PS) were calculated to indicate independent factors associated with the use of induction. Levels of HLA match examined for DD transplant recipients were 0 ABDR (n = 3239), 0 DR (n = 4210), and DR mismatched transplants (n = 12,980), and 0 (n = 1133), 1 (n = 3836), and 2 (n = 7890) haplotype mismatches for LD transplant recipients. Outcome parameters were reported as hazard ratios (HR) for graft loss and odds ratios (OR) for first-year acute rejection. RESULTS: Recipients with HLA mismatches were more likely to receive induction antibody for DR mismatch in DDs (PS = 1.11, 95% confidence interval [CI] 1.04-1.19) and for haplotype mismatch in LDs (PS = 1.36, 95% CI 1.22-1.52). Induction reduced the likelihood of acute rejection for DD transplant recipients regardless of the level of HLA mismatch (OR = 0.70; 95% CI 0.57-0.85 in 0 ABDR MM; OR = 0.76, 95% CI 0.64-0.89 in 0 DR MM; and OR = 0.69, 95% CI 0.62-0.77 in DR MM), and for 2 haplotype mismatched LD transplant recipients (OR = 0.82, 95% CI 0.70-0.96); in other LD transplant recipients, reductions in acute rejection rates were observed but not statistically significant. Induction reduced the risk of graft loss for DR mismatched DD transplant recipients by about 12% (HR = 0.88; 95% CI 0.80-0.97). CONCLUSIONS: Antibody induction resulted in a significant reduction of acute rejection and graft loss for patients with HLA mismatch.

Antibody Formation↗
PubMed2005

Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models.

In this study, we report the amelioration of parkinsonian symptoms in rat Parkinson's disease (PD) models, as a result of the expression of glutamate decarboxylase (GAD) 65 with a modified cytomegalovirus (CMV) promoter. The transfer of the gene for gamma-amino butryic acid (GAD), the rate-limiting enzyme in gama-amino butrylic acid (GABA) production, has been investigated as a means to increase inhibitory synaptic activity. Electrophysiological evidence suggests that the transfer of the GAD65 gene to the subthalamic nucleus (STN) can change the excitatory output of this nucleus to inhibitory output. Our in vitro results also demonstrated higher GAD65 expression in cells transfected with the JDK promoter, as compared to cells transfected with the CMV promoter. Also, a rat PD model in which recombinant adeno-associated virus-2 (rAAV2)-JDK-GAD65 was delivered into the STN exhibited significant behavioral improvements, as compared to the saline-injected group. Interestingly, we observed that these behavioral improvements were more obvious in rat PD models in which rAAV2-JDK-GAD65 was injected into the STN than in rat PD models in which rAAV2-CMV-GAD65 was injected into the STN. Moreover, according to electrophysiological data, the rAAV2-JDK-GAD65-injected group exhibited more constant improvements in firing rates than did the rAAV2-CMV-GAD65-injected group. These data indicate that the JDK promoter, when coupled with GAD65 expression, is more effective with regard to parkinsonian symptoms than is the CMV promoter.

Adenoviridae↗
PubMed2004

Pharmacological interventions for treating acute heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) is the formation of mature lamellar bone in soft tissue sites outside the skeleton. HO frequently complicates burns, arthroplasty, fractures, and spinal cord and brain injuries. It can impair joint function. OBJECTIVES: To determine the efficacy of medications to treat acute HO on radiological, symptomatic, functional impairment, and disability outcomes. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to August 2004), CINAHL (1982 to August 2004), other databases, reference lists of articles, and contacted trialists and drug companies. No language restrictions were applied. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials that assessed the efficacy of any medication for treating acute HO (confirmed by bone scintigraphy, radiography, ultrasonography, or biopsy) and which used radiography to grade post-treatment HO severity. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the study quality and extracted data. We analysed two dichotomous outcomes: no progression in HO grade (versus progression) and improvement in HO grade (versus no improvement). MAIN RESULTS: Two randomised trials comparing disodium etidronate versus placebo were included (Ono 1988; Stover 1976), from which ninety-two participants with spinal cord injury had radiographically-proven HO at baseline. At the completion of the 12 week intervention, the Ono study but not the Stover study, suggested that disodium etidronate was associated with a significantly greater likelihood of successfully preventing the progression of radiographic HO grade, (relative risk (RR) 1.50; 95% confidence interval (CI) I 1.16 to 1.93; and RR 1.48; 95% CI 0.78 to 2.84 respectively) and a significantly greater likelihood of improvement in HO grade (RR 2.78; 95% CI 1.66 to 4.66; and RR 0.71; 95% CI 0.20 to 2.53 respectively). There was evidence of statistical heterogeneity for the latter outcome. Longer term radiographic, clinical or side effect outcomes were unavailable. Data was not pooled due to this heterogeneity and the inadequate duration of follow up. REVIEWERS' CONCLUSIONS: Given the absence of long term radiographic outcomes in the included studies, there is insufficient evidence to recommend the use of disodium etidronate or other pharmacological agents for the treatment of acute HO. It has been previously suggested that disodium etidronate acts by delaying, rather than preventing, the mineralization of HO, and that mineralization may occur after treatment cessation in many cases, thereby negating the benefit of disodium etidronate on eventual HO grade. Further studies are required to assess all pharmacological treatments for acute HO with sufficient follow-up duration.

Etidronic Acid↗
PubMed2004

Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans.

Impairments in early information processing are a hallmark feature of diverse neuropsychiatric disorders including schizophrenia and Alzheimer's disease (AD). Several lines of evidence implicate a dysfunction of the cholinergic system in these disorders, particularly in AD where there is known degeneration in major cholinergic pathways. Inspection time (IT), a measure of early visual information processing speed, has been shown to be sensitive to cholinergic manipulation. The current study employed the IT task to (1) examine the independent roles of nicotinic and muscarinic receptors in modulating information processing and (2) investigate the interaction of nicotinic and muscarinic receptor systems in modulating information processing. Twelve healthy participants completed a randomized, double-blind, placebo-controlled study under four drug conditions; (1) placebo, (2) mecamylamine (15 mg; oral), (3) scopolamine (0.4 mg, s.c.), (4) mecamylamine (15 mg) + scopolamine (0.4 mg). IT measures were examined at baseline and 2.5 h post drug administration. Selective blockade of nicotinic receptors with mecamylamine did not significantly impair IT, whereas selective blockade of muscarinic receptors with scopolamine produced a significant but small impairment in IT. Combined blockade of both receptor types with scopolamine and mecamylamine produced a large impairment in IT performance. The results indicate that both nicotinic and muscarinic receptors are involved in modulating IT, and that the two systems may function synergistically to modulate early visual information processing. These findings suggest that functional abnormalities in both nicotinic and muscarinic systems may underlie deficits in early visual information processing seen in disorders such as Alzheimer's disease and schizophrenia.

Adult↗
PubMed2004

Identifying the psychosocial correlates of condom use by female sex workers in Hong Kong.

This study examined factors affecting condom use by Hong Kong female sex workers when they have sex with their clients and steady partners. Our respondents consisted of 109 active female sex workers, mainly streetwalkers or sex workers who worked in villas. During a 30-minute interview, respondents were interviewed individually and were asked questions regarding their condom use practice. These questions were designed to measure various factors affecting their condom use practice, including attitudes toward condom use, normative pressure, perceived behavioural control, perceived AIDS risks, past condom use behaviour, and future condom use intentions with respect to the two types of partners. Multiple regression analyses reveal that perceived behavioural control is the most important factor associated with these respondents' future condom use across the two types of partners. Perceived AIDS risk is the additional predictor for condom use with clients, while normative pressure is the additional predictor for condom use with steady partners. Past condom use behaviour also provided significant additional prediction for both types of partners, implying the habitual nature of condom use among our respondents. These results have significant implications for designing intervention programmes targeting at increasing condom use by female sex workers in Hong Kong.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Effects of Lactobacilli and an acidophilic fungus on the production performance and immune responses in broiler chickens.

Accumulated lines of evidence indicate that inactivated probiotics could have beneficial effects similar to those of live probiotics. Two strains of disrupted, cobalt-enriched, lactic acid bacteria (Lactobacillus acidophilus and Lactobacillus casei) and a disrupted fungal mycelium (Scytalidium acidophilum) were spray-mixed onto a mash basal feed, in 2 concentrations, prior to pelleting. The effects of these probiotics on production performance and immune response in broiler chickens were investigated. The production parameters, including BW, feed intake (FI), BW gain (BWG), and feed conversion ratio (FCR), were monitored weekly during a 6-wk trial. The immune response was evaluated by immunizing the birds with the antigen keyhole limpet hemocyanin (KLH) followed by a serological assay to measure blood IgA and IgG titers. Some of the production parameters were significantly improved by low L. casei (LCL; for BW and BWG), high L. acidophilus (LAH; for BW and BWG), and high fungal (FH; for BW, BWG, and FI) in comparison with the nonadditive control (NC-). However, these 3 treatments (LCL, LAH, and FH) did not enhance the measured immune responses. Instead, the titers of serum KLH-specific IgA in high L. casei (LCH) and low L. acidophilus (LAL) were significantly higher than those of NC-, 10 d after immunization. None of the probiotic treatments increased the titer of KLH-specific IgG in blood. Our results indicate that disrupted and cobalt-enriched L. acidophilus or L. casei was able to enhance production performance of broiler chickens. The fungal mycelium, S. acidophilum, when used at a high concentration, also demonstrated its potential for the first time to be used as a probiotic. In addition, the optimal concentration for administering probiotics is strain dependent. A higher dose does not always result in a better performance.

Animal Nutritional Physiological Phenomena↗