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Biomedical subjects

H Lee

Publications and source records attributed to H Lee.

At least 37 records · Page 2Linked to original sources
PubMed2006

Eye-movement responses to disparity vergence stimuli with artificial monocular scotomas.

The effects of artificial monocular scotomas on eye-movement responses to horizontal disparity vergence stimuli were studied in six subjects with normal binocular vision. Subjects viewed stereoscopic 1.5 degrees horizontal step disparity vergence stimuli through liquid crystal shutter glasses. The central portion of the stimulus presented to the right eye was removed to simulate monocular artificial scotomas of variable diameters (2 degrees to 10 degrees ). Eye movements were recorded with a binocular head-mounted eye tracker. Responses included pure vergence, vergence followed by saccades, and pure saccadic eye movements. The rate of responses with saccadic eye movements increased with the diameter of the artificial scotoma (p < 0.0001); there was an increase in the rate of responses starting with saccades (p < 0.0001), as well as an increase in the rate of saccades after initial vergence responses (p < 0.01). The probability of saccades after initial vergence responses was affected by the open-loop gain of the vergence response (p < 0.001). The open-loop gain decreased with increased diameters of the artificial scotomas (p < 0.0001). As the diameter of the artificial scotomas increased, the amplitude of the initial vergence eye-movement responses decreased, and the prevalence of saccadic eye movements and asymmetric vergence increased. The effects of the diameter of artificial monocular scotomas on eye-movement responses in subjects with normal binocular vision are consistent with the effects of diameter of suppression scotomas on eye-movement responses to disparity vergence stimuli in patients with infantile esotropia.

Adolescent↗
PubMed2006

The effects of the exaggerated lithotomy position for radical perineal prostatectomy on respiratory mechanics.

The exaggerated lithotomy position is used during radical perineal prostatectomy to increase perineal exposure. The aim of this study was to evaluate the effects of the exaggerated lithotomy position on respiratory mechanics and arterial blood gases. In the exaggerated lithotomy position, dynamic compliance and static compliance were found to be significantly decreased by 27.4% and 34.8%, respectively, whilst peak, plateau, and mean airway pressures increased significantly by 34.0%, 45.8% and 31.7%, respectively. The physiological dead space/tidal volume ratio and total inspiratory work of breathing increased significantly by 11.1% and 33.7%, respectively. Arterial oxygen tension was significantly decreased by 26.9%; however, no significant differences were seen in end-tidal or arterial carbon dioxide tension. These results indicate that the exaggerated lithotomy position under general anaesthesia can cause significant effects on respiratory system mechanics and arterial oxygenation and highlights the need for careful monitoring of patients placed in this position for surgery.

Aged↗
PubMed2006

Core temperature and hydration status during an Ironman triathlon.

BACKGROUND: Numerous laboratory based studies have documented that aggressive hydration strategies (approximately 1-2 litres/h) are required to minimise a rise in core temperature and minimise the deleterious effects of hyperthermia on performance. However, field data on the relations between hydration level, core body temperature, and performance are rare. OBJECTIVE: To measure core temperature (Tcore) in triathletes during a 226 km Ironman triathlon, and to compare Tcore with markers of hydration status after the event. METHOD: Before and immediately after the 2004 Ironman Western Australia event (mean (SD) ambient temperature 23.3 (1.9) degrees C (range 19-26 degrees C) and 60 (14)% relative humidity (44-87%)) body mass, plasma concentrations of sodium ([Na+]), potassium ([K+]), and chloride ([Cl-]), and urine specific gravity were measured in 10 well trained triathletes. Tcore was measured intermittently during the event using an ingestible pill telemetry system, and heart rate was measured throughout. RESULTS: Mean (SD) performance time in the Ironman triathlon was 611 (49) minutes; heart rate was 143 (9) beats/min (83 (6)% of maximum) and Tcore was 38.1 (0.3) degrees C. Body mass significantly declined during the race by 2.3 (1.2) kg (-3.0 (1.5)%; p < 0.05), whereas urine specific gravity significantly increased (1.011 (0.005) to 1.0170 (0.008) g/ml; p < 0.05) and plasma [Na+], [K+], and [Cl-] did not change. Changes in body mass were not related to finishing Tcore (r = -0.16), plasma [Na+] (r = 0.31), or urine specific gravity (r = -0.37). CONCLUSION: In contrast with previous laboratory based studies examining the influence of hypohydration on performance, a body mass loss of up to 3% was found to be tolerated by well trained triathletes during an Ironman competition in warm conditions without any evidence of thermoregulatory failure.

Adult↗
PubMed2006

Self-organized monolayer formation from binary mixtures of substituted alkyl chains studied by STM.

The molecular assembly of p-iodo-phenyl octadecyl ether (I-POE), p-iodo-phenyl docosyl ether (I-PDE) and a binary mixture of these two molecules on graphite has been studied using a scanning tunneling microscope. Each molecular system self-assembles on the graphite surface to form a stable monolayer. For the binary system, the I-POE and I-PDE molecules do not mix on the surface, preferring instead to form isolated monolayer domains. Here, the I-POE molecules are preferentially adsorbed on the graphite surface, due to the effects of alkyl chain length and the functional group on the monolayer structure.

Adsorption↗
PubMed2006

Observation and quantification of cavitation on a mechanical heart valve with an electro-hydraulic total artificial heart.

In previous studies, we investigated the cavitation phenomenon in a mechanical heart valve using an electro-hydraulic total artificial heart. With this system, a 50% glycerin solution kept at 37 degrees C was used as the working fluid. We reported that most of the cavitation bubbles were observed near the valve stop and were caused by the squeeze flow. However, in these studies, the effect of the partial pressure of CO(2) on the mechanical heart valve cavitation was neglected. In this study, in order to investigate the effect of the partial pressure of CO(2) on mechanical heart valve cavitation using an electro-hydraulic total artificial heart, we controlled the partial pressure of the CO(2) in vitro. A 25-mm Medtronic Hall valve was installed in the mitral position of an electro-hydraulic total artificial heart. In order to quantify the mechanical heart valve cavitation, we used a high-speed camera. Even though cavitation intensity slightly increased with increases in the PCO(2) at heart rates of 60, 70 and 100 bpm, throughout the experiment, there was no significant difference between the PCO(2) and cavitation intensity.

Electricity↗
PubMed2006

Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.

Adult↗
PubMed2006

Formulation of drugs in block copolymer micelles: drug loading and release.

Block copolymer micelles have become accepted as a viable strategy for drug formulation and delivery. Block copolymer micelles may serve as solubilizers and/or true drug carriers depending on their drug retention properties in vivo. Indeed the formulation of hydrophobic drugs in these micelle systems has been shown to provide up to a 30,000 fold increase in the water solubility of some compounds. In addition, the administration of drugs in copolymer micelles has been shown to reduce their toxicity and improve their therapeutic efficacy. The present review is focused on the drug loading and release properties of block copolymer micelles. Specifically, the properties of the drug, properties of the micelle core and the presence of interactions between the drug and the core-forming block are discussed in terms of their influence on the drug loading and release properties of the micelles. The various methods employed to prepare drug-loaded micelles are reviewed and the in vitro release assays used to predict the in vivo release characteristics of the formulations are discussed. The balance between drug loading and micelle stability is highlighted as a critical factor in the optimization of micelle-based formulations. The in vivo performance of micelles as delivery systems is evaluated by comparing the pharmacokinetics of free drug and drug administered in micelle-based formulations. Overall, the composition-property and property-performance relationships outlined in this review may aid in guiding the rational design of block copolymer micelles for drug delivery. In addition, suggestions for future research in this area are provided as a means to assist in furthering block copolymer micelles as one of the leading advanced drug delivery technologies for the systemic administration of drugs.

Animals↗
PubMed2005

Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo.

Microtubule binding protein Tau was recently identified through gene expression analysis of human breast cancer tissues as a novel marker of response to paclitaxel. This article reviews these recent findings and provides additional information to support the role of Tau as an emerging marker and mediator of paclitaxel sensitivity. Low expression of Tau is associated with increased sensitivity to paclitaxel in human breast cancer as well as in a broad range of cell lines. Down regulation of Tau in cell lines by siRNA increases their sensitivity to paclitaxel but not to anthracycline chemotherapy. We propose that this is due to increased paclitaxel binding to microtubules when microtubules are assembled in the presence of low concentrations (or absence) of Tau compared to microtubules that are formed in the presence of physiological (or higher) levels of Tau.

Alternative Splicing↗
PubMed2005

New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid arthritis receiving tumour necrosis factor alpha antagonists.

BACKGROUND: Blockage of tumour necrosis factor alpha (TNFalpha) is highly effective in rheumatic diseases, especially in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Furthermore, TNFalpha antagonists have also been shown to significantly reduce psoriatic skin lesions. CASE REPORTS: A series of nine patients with RA who were treated with different types of TNFalpha antagonists and who unexpectedly developed either a new onset or an exacerbation of psoriatic skin lesions are reported.

Adalimumab↗
PubMed2005

Fluorescent methods to study DNA, RNA, proteins and cytoplasmic membrane polarization in the pentachlorophenol-mineralizing bacterium Sphingomonas sp. UG30 during nutrient starvation in water.

The effect of sodium pentachlorophenolate (NaPCP) exposure on the nutrient-starved pentachlorophenol (PCP)-mineralizing bacterium Sphingomonas sp. UG30 was assessed using fluorescent methods to measure DNA, RNA, total cellular protein, and cytoplasmic membrane proteins. UG30 cells were inoculated into sterilized Speed River (Guelph, ON, Canada) water samples in the presence of 50, 100, and 250 ppm NaPCP. No marked changes were observed in the total cellular DNA, RNA or protein levels over 90 d, indicating the macromolecular composition of UG30 was not affected by both nutrient limitation and NaPCP. Total cell counts as determined by DAPI staining also did not change over 90 d. Over the same period, viable counts decreased with increasing concentrations of NaPCP. At 250 ppm NaPCP, viable cell counts decreased over 6 orders of magnitude after 1 hr exposure. Cell numbers partially recovered once NaPCP was degraded. The UG30 cytoplasmic membrane polarization ratio also decreased after NaPCP was depleted. The decreased polarization value at the end of the study period suggested the UG30 membrane was more fluid and that this increase in fluidity was due to nutrient starvation effects rather than exposure to NaPCP. These results indicated that UG30 is a robust organism that is able to degrade NaPCP even under adverse conditions and fluorescent methods are useful for determining macromolecular concentrations and cytoplasmic membrane polarization values.

Bacterial Proteins↗
PubMed2005

A pharmacokinetic-pharmacodynamic model for the mobilization of CD34+ hematopoietic progenitor cells by AMD3100.

BACKGROUND: AMD3100 is a small-molecule CXCR4 antagonist that has been shown to induce the mobilization of CD34 + hematopoietic progenitor cells from bone marrow to peripheral blood. AMD3100 has also been shown to augment the mobilization of CD34 + cells in cancer patients when administered in combination with granulocyte colony-stimulating factor (G-CSF) (filgrastim). The purpose of this study was to characterize the exposure-response relationship of AMD3100 in mobilizing CD34 + cells when administered as a single agent in healthy volunteers. METHODS: AMD3100 concentrations and CD34 + cell counts obtained from 29 healthy subjects in a single-dose, intensively sampled pharmacokinetic/pharmacodynamic (PK-PD) study were analyzed by use of nonlinear mixed effects regression with the software NONMEM. FOCE (first order conditional estimation) with interaction was the estimation method, and simultaneous PK-PD fitting was adopted. RESULTS: The pharmacokinetics of AMD3100 was described by a 2-compartment model with first-order absorption. The population estimates (+/-SE) for clearance and central volume of distribution were 5.17 +/- 0.49 L/h and 16.9 +/- 3.79 L, respectively. CD34 + cell mobilization was best described by an indirect effect model that stimulates the entry process of CD34 + from bone marrow to peripheral blood in the form of a sigmoid maximum effect model. The population estimates (+/-SE) of maximum effect, concentration causing 50% of maximum response, and equilibration time were 12.6 +/- 4.89, 53.6 +/- 11.9 mug/L, and 5.37 +/- 1.31 hours, respectively. CONCLUSIONS: This study characterizes the exposure-response relationship of AMD3100 in mobilizing CD34 + cells after subcutaneous administration. This PK-PD model will be useful in assessing relevant covariates and for optimizing the use of AMD3100 in various patient populations.

Adult↗
PubMed2005

Shigellosis remains an important problem in children less than 5 years of age in Thailand.

This is a review of existing data on the burden of shigellosis in Thailand to determine trends, vulnerable groups, predominant species and serotypes, and antimicrobial resistance patterns. Diarrhoea and dysentery morbidity and mortality data from 1991 to 1999 was collected from the routine surveillance system and demographic data from the government census. International and local literature published between 1988 and 2000 was systematically reviewed. Based on the routine surveillance system, the annual incidence of bacillary dysentery decreased from 1.3 to 0.2/10,000 persons per year. The remaining burden is highest in children <5 years of age at 2.7/10,000 persons per year. In comparison, a prospective study utilizing active surveillance found an incidence in children <5 years of age that was more than 100-fold higher at 640/10,000 persons per year. Despite the decrease in morbidity and mortality based on routinely collected data, shigellosis remains an important problem in children <5 years of age in Thailand.

Child Health Services↗
PubMed2005

Evaluation of TNF-alpha and IL-1beta polymorphisms in Taiwan Chinese patients with pterygium.

PURPOSE: Pterygium, a complex disease, is associated with ultraviolet radiation, immunoinflammatory process, genetic factors, and virus infection. Ultraviolet radiation induces secretion of proinflammatory cytokines by the ocular surface epithelium, inflammatory cells in the tear fluid, or both. Among these cytokines, tumour necrosis factor (TNF)alpha and interleukin (IL)-1beta activate pterygium body fibroblasts, resulting in a phenotype capable of expressing various proteinases associated with extracellular matrix remodelling, angiogenesis, and fibroblast proliferation, which are important for pterygium formation and recurrence. The genetic factor was proposed to play a role in pterygium formation, but there were few studies to clarify this proposition. For investigating genetic factors, the association between pterygium and TNF-alpha and IL-1beta polymorphisms is evaluated in this study. METHODS: A total of 128 pterygium patients and 103 volunteers without pterygium were enrolled in this study. Polymerase chain reaction-based analysis was used to resolve the TNF-alpha-308 promoter, IL-1beta-511 promoter, IL-1beta exon 5, and IL-1 receptor antagonist (IL-1 Ra) polymorphisms. RESULTS: There were no significant differences in the frequency of genotypes and alleles of TNF-alpha-308 promoter, IL-1beta-511 promoter, IL-1beta exon 5, and IL-1 Ra polymorphisms between both groups. CONCLUSIONS: The correlation between pterygium and TNF-alpha-308 promoter, IL-1beta-511 promoter, IL-1beta exon 5, and IL-1 Ra polymorphisms does not exist and those polymorphisms are not useful genetic markers for pterygium susceptibility. Further studies on other polymorphisms or haplotypes of TNF-alpha and IL-1beta are necessary.

Adult↗
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↗
PubMed2005

Gene delivery to human sweat glands: a model for cystic fibrosis gene therapy.

Gene therapy vectors are mostly studied in cultured cells, rodents, and sometimes in non-human primates, but it is useful to test them in human tissue prior to clinical trials. In this study, we investigated the possibility of using human sweat glands as a model for testing cystic fibrosis (CF) gene therapy vectors. Human sweat glands are relatively easy to obtain from skin biopsy, and can be tested for CFTR function. Using patients' sweat glands could provide a safe model to study the efficacy of CF gene therapy. As the first step to explore using sweat glands as a model for CF gene therapy, we examined various ex vivo gene delivery methods for a helper-dependent adenovirus (HD-Ad) vector. Gene delivery to sweat glands in skin organ culture was studied by topical application, intradermal injection or submerged culture. We found that transduction efficiency can be enhanced by pretreating isolated sweat glands with dispase, which suggests that the basement membrane is a critical barrier to gene delivery by adenoviral vectors. Using this approach, we showed that Cftr could be efficiently delivered to and expressed by the epithelial cells of sweat glands with our helper-dependent adenoviral vector containing cytokeratin 18 regulatory elements. Based on this study we propose that sweat glands might be used as an alternative model to study CF gene therapy in humans.

Adenoviridae↗
PubMed2005

Calreticulin expression in neuroblastoma--a novel independent prognostic factor.

BACKGROUND: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. PATIENTS AND METHODS: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. RESULTS: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (< or =1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan-Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. CONCLUSIONS: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.

Biomarkers, Tumor↗