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Biomedical subjects

Sang Hyun Cho

Publications and source records attributed to Sang Hyun Cho.

13 recordsLinked to original sources

Comparison between an event-by-event Monte Carlo code, NOREC, and ETRAN for electron scaled point kernels between 20 keV and 1 MeV.

An event-by-event Monte Carlo code called NOREC, a substantially improved version of the Oak Ridge electron transport code (OREC), was released in 2003, after a number of modifications to OREC. In spite of some earlier work, the characteristics of the code have not been clearly shown so far, especially for a wide range of electron energies. Therefore, NOREC was used in this study to generate one of the popular dosimetric quantities, the scaled point kernel, for a number of electron energies between 0.02 and 1.0 MeV. Calculated kernels were compared with the most well-known published kernels based on a condensed history Monte Carlo code, ETRAN, to show not only general agreement between the codes for the electron energy range considered but also possible differences between an event-by-event code and a condensed history code. There was general agreement between the kernels within about 5% up to 0.7 r/r (0) for 100 keV and 1 MeV electrons. Note that r/r (0) denotes the scaled distance, where r is the radial distance from the source to the dose point and r (0) is the continuous slowing down approximation (CSDA) range of a mono-energetic electron. For the same range of scaled distances, the discrepancies for 20 and 500 keV electrons were up to 6 and 12%, respectively. Especially, there was more pronounced disagreement for 500 keV electrons than for 20 keV electrons. The degree of disagreement for 500 keV electrons decreased when NOREC results were compared with published EGS4/PRESTA results, producing similar agreement to other electron energies.

Electrons↗

Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis.

Screening for new antimicrobial agents is routinely conducted only against actively replicating bacteria. However, it is now widely accepted that a physiological state of nonreplicating persistence (NRP) is responsible for antimicrobial tolerance in many bacterial infections. In tuberculosis, the key to shortening the 6-month regimen lies in targeting this NRP subpopulation. Therefore, a high-throughput, luminescence-based low-oxygen-recovery assay (LORA) was developed to screen antimicrobial agents against NRP Mycobacterium tuberculosis. M. tuberculosis H37Rv containing a plasmid with an acetamidase promoter driving a bacterial luciferase gene was adapted to low oxygen conditions by extended culture in a fermentor with a 0.5 headspace ratio. The MICs of 31 established antimicrobial agents were determined in microplate cultures maintained under anaerobic conditions for 10 days and, for comparative purposes, under aerobic conditions for 7 days. Cultures exposed to drugs under anaerobic conditions followed by 28 h of "recovery" under ambient oxygen produced a luminescent signal that was, for most compounds, proportional to the number of CFU determined prior to the recovery phase. No agents targeting the cell wall were active against NRP M. tuberculosis, whereas drugs hitting other cellular targets had a range of activities. The calculated Z' factor was in the range of 0.58 to 0.84, indicating the suitability of the use of LORA for high-throughput assays. This LORA is sufficiently robust for use for primary high-throughput screening of compounds against NRP M. tuberculosis.

Anti-Bacterial Agents↗

Synthesis and antitubercular activity of quaternized promazine and promethazine derivatives.

Quaternized chlorpromazine, triflupromazine, and promethazine derivatives were synthesized and examined as antitubercular agents against both actively growing and non-replicating Mycobacterium tuberculosis H37Rv. Impressively, several compounds inhibited non-replicating M. tuberculosis at concentrations equal to or double their MICs against the actively growing strain. All active compounds were non-toxic toward Vero cells (IC50 > 128 microM). N-Allylchlorpromazinium bromide was only weakly antitubercular, but replacing allyl with benzyl or substituted benzyl improved potency. An electron-withdrawing substituent on the phenothiazine ring was also essential. Branching at the carbon chain decreased antitubercular activity. The optimum antitubercular structures possessed N-(4- or 3-chlorobenzyl) substitution on triflupromazine.

Antitubercular Agents↗

Ethnopharmacological evaluation of the informant consensus model on anti-tuberculosis claims among the Manus.

Ethnobotanists often utilize predictive models to analyze the potential of indigenously used medicinal plants. The most common of these prognostic models is the informant consensus model. This study evaluates use of this model through the analytical ethnopharmacology of Manus Province, Papua New Guinea (PNG). The informant consensus model enables researchers to prioritize plants for pharmacognostic evaluation, based on the relative frequency of plants cited in anthropological interviews. Fieldwork on Manus Island, PNG, led to the identification of 43 species of plants used in traditional medicine for persistent respiratory symptoms. Plants were collected, dried, micro-extracted using a new technique generated in our laboratory, and evaluated in vitro against Mycobacterium tuberculosis. The results, in the form of IC(50) values and modified selectivity indices (SI), were compared to the results of the anthropological models of informant consensus, and statistically compared through linear regression and t-tests. Results were not statistically significant (alpha=0.1), leading to the conclusions that the informant consensus assumptions were inaccurate in predicting anti-mycobacterial activity among the Manus for anti-TB claims.

Anti-Bacterial Agents↗

Role of bacterial superantigens in atopic dermatitis : implications for future therapeutic strategies.

The role of staphylococcal superantigens in the pathophysiology of atopic dermatitis (AD) has been the focus of intense interest during the past decade. Although the increased prevalence of Staphylococcus aureus and its bacterial toxins in AD skin is well established, exploitation of the known mechanisms of superantigens in this disease for the development of novel therapies remains an active area of research. With the emergence of multi-drug resistant S. aureus, the need for a better understanding of the pathophysiology of bacterial superantigens in AD has become increasingly important. This review examines the mechanisms of S. aureus colonization and infection, of which the most important are defective skin barrier function, increased S. aureus adherence, and the decreased innate immune responses found in AD skin. The contribution of superantigens to the pathophysiology of AD is then discussed. Important immunologic mechanisms in this context include the role of superantigens in promoting T helper-2 skin inflammation, IgE production, T-regulatory cell subversion, expansion and migration of skin-homing T cells, and IgE anti-superantigen production. Lastly, these findings are discussed with reference to current therapeutic approaches, of which the most important include anti-inflammatory and antimicrobial medications, and future strategies, which are expected to consist of immune-modulators and synthetic antibacterials.

Animals↗

ICAT-based comparative proteomic analysis of non-replicating persistent Mycobacterium tuberculosis.

The non-replicating persistence (NRP) phenotype of Mycobacterium tuberculosis (NRP-TB) is assumed to be responsible for the maintenance of latent infection and the requirement of a long treatment duration for active tuberculosis. Isotope coded affinity tag-based proteomic analysis was used for the determination of the relative expression of large numbers of M. tuberculosis proteins during oxygen self-depletion under controlled conditions in a multi-chambered fermentor. Expression of the alpha-crystallin homolog protein, acr, was monitored and quantified to confirm entry into NRP. Relative expression of 586 and 628 proteins was determined in log phase vs. early stage NRP (NRP-1) and log phase vs. later stage NRP (NRP-2), respectively. Relative to expression in log phase and using an abundance ratio of +/-2.0 as a cutoff, 6.5% and 20.4% of proteins were found to be upregulated in NRP-1 and NRP-2, respectively while 20.3% and 13.4% were downregulated, respectively. Functional profiling revealed that 42.1%/39.8% of upregulated proteins and 41.2%/45.2% of downregulated proteins in NRP-1/NRP-2, respectively, were involved in small molecule metabolism. Among those proteins the highest proportions of 37.5% in NRP-1 were involved with degradation and of 45.1% in NRP-2 with energy metabolism. These results suggest distinct protein expression profiles in NRP-1 and NRP-2.

Bacterial Proteins↗

PRDC--a software package for personnel radiation dose calculation.

To determine effective dose, we usually need to use a very complicated human body model and a sophisticated computer code to transport radiations in the body model and surrounding medium, which is not very easy to practicing health physicists in the field. This study develops and tests a software package, called PRDC (Personnel Radiation Dose Calculation), which calculates effective dose and radiation doses to various organs/tissues and personal dosemeters based on a series of interpolations.

Algorithms↗

Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: a preliminary Monte Carlo study.

A recent mice study demonstrated that gold nanoparticles could be safely administered and used to enhance the tumour dose during radiation therapy. The use of gold nanoparticles seems more promising than earlier methods because of the high atomic number of gold and because nanoparticles can more easily penetrate the tumour vasculature. However, to date, possible dose enhancement due to the use of gold nanoparticles has not been well quantified, especially for common radiation treatment situations. Therefore, the current preliminary study estimated this dose enhancement by Monte Carlo calculations for several phantom test cases representing radiation treatments with the following modalities: 140 kVp x-rays, 4 and 6 MV photon beams, and 192Ir gamma rays. The current study considered three levels of gold concentration within the tumour, two of which are based on the aforementioned mice study, and assumed either no gold or a single gold concentration level outside the tumour. The dose enhancement over the tumour volume considered for the 140 kVp x-ray case can be at least a factor of 2 at an achievable gold concentration of 7 mg Au/g tumour assuming no gold outside the tumour. The tumour dose enhancement for the cases involving the 4 and 6 MV photon beams based on the same assumption ranged from about 1% to 7%, depending on the amount of gold within the tumour and photon beam qualities. For the 192Ir cases, the dose enhancement within the tumour region ranged from 5% to 31%, depending on radial distance and gold concentration level within the tumour. For the 7 mg Au/g tumour cases, the loading of gold into surrounding normal tissue at 2 mg Au/g resulted in an increase in the normal tissue dose, up to 30%, negligible, and about 2% for the 140 kVp x-rays, 6 MV photon beam, and 192Ir gamma rays, respectively, while the magnitude of dose enhancement within the tumour was essentially unchanged.

Animals↗

Reference photon dosimetry data and reference phase space data for the 6 MV photon beam from varian clinac 2100 series linear accelerators.

The current study presents the reference photon dosimetry data (RPDD) and reference phase space data (RPSD) for the 6 MV photon beam from Varian 2100 series linear accelerators. The RPDD provide the basic photon dosimetry data, typically collected during the initial commissioning of a new linear accelerator, including output factors, depth dose data, and beam profile data in air and in water. The RPSD provide the full phase space information, such as position, direction, and energy for each particle generated inside the head of any particular linear accelerator in question. The dosimetric characteristics if the 6 MV photon beam from the majority of the aforementioned accelerators, which are unaltered from the manufacturer's original specifications, can be fully described with these two data sets within a clinically acceptable uncertainty (approximately +/-2 %). The current study also presents a detailed procedure to establish the RPDD and RPSD using measured data and Monte Carlo calculations. The RPDD were constructed by compiling our own measured data and the average data based on the analysis of more than 50 sets of measured data from the Radiological Physics Center (RPC) and 10 sets of clinical dosimetry data obtained from 10 different institutions participating in the RPC's quality assurance monitoring program. All the measured data from the RPC and the RPC-monitored institutions were found to be within a statistically tight range (i.e., 1sigma approximately 1% or less) for each dosimetric quantity. The manufacturer's standard data, except for in-air off-axis factors that are available only from the current study, were compared with the RPDD, showing that the manufacturer's standard data could also be used as the RPDD for the photon beam studied in this study. The RPSD were obtained from Monte Carlo calculations using the BEAMnrc/ DOSXYZnrc code system with 6.2 MeV (a spread of 3% full width at half maximum) and 1.0 mm full width at half maximum as the values of the energy and radial spread of a Gaussian electron pencil beam incident on the target, respectively. The RPSD were capable of generating Monte Carlo data that agreed with the RPDD within the acceptance criteria adopted in the current study (e.g., 1% or 1 mm for depth dose). A complete set of the RPDD and RPSD from the current study is available from the RPC website (http://rpc.mdanderson.org) or via mass storage media such as DVD or CD-ROM upon request.

Electrons↗

Anthropomorphic breast phantoms for quality assurance and dose verification.

An evaluation of two anthropomorphic breast phantoms, which have been designed for quality assurance and dose verification of radiotherapy treatment of breast cancer patients, is presented. These phantoms are identical in terms of their dimensions and shape, and composed of several layers of either Plastic Water or tissue-equivalent material. Both water- and tissue-equivalent phantoms include lung- and rib-equivalent components. The phantoms simulate large, medium and small breasts. The value of the phantoms as breast treatment quality assurance tools was assessed by dose measurements with ionization chamber and thermoluminescence dosimeters (TLD), at different points inside the phantom. Measurements were made by irradiating the phantoms under conditions representing the different treatment techniques, found by the Radiological Physics Center (RPC) during its dosimetry quality audits. Most irradiations were performed with the water-equivalent breast phantom. One experiment was performed under consistent irradiation conditions to compare the tissue-equivalent phantom with the water-equivalent phantom. Measurements were compared with the dose estimated by the RPC's manual calculations used to check clinical charts of patients entered in a National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol. Measurements were also compared with isodose distributions generated by a commercial radiation treatment planning (RTP) system. In the homogeneous three-dimensional (3-D) phantom, fairly good agreement (within 5%) was observed at the NSABP dose prescription point between measurements and 2-D dose estimation by manual calculations. At the same dose prescription point, but located in the heterogeneous 3-D phantom, agreement between measurements and a 3-D RTP system was within about 3%. Manual calculation resulted in overestimation of up to 6%. The general agreement between the TLD measurements and the 2-D RTP values was within 3% at various off-axis points, with the exception of a few points far off-axis, near the high-dose gradient region at the surface of the phantom.

Anthropometry↗

Crystallization and preliminary X-ray crystallographic analysis of the Rv2002 gene product from Mycobacterium tuberculosis, a beta-ketoacyl carrier protein reductase homologue.

A 260-residue protein (FabG3) encoded by the Rv2002 gene of Mycobacterium tuberculosis shows amino-acid sequence similarity to beta-ketoacyl carrier protein (ACP) reductase, FabG. A soluble mutant (I6T/V47M/T69M) was produced by the green fluorescent protein-based directed-evolution method. It was crystallized at 296 K using the hanging-drop vapour-diffusion method. The diffraction quality of the crystal improved significantly after annealing/dehydration. X-ray diffraction data were collected to 1.8 A resolution using synchrotron radiation. The crystal belongs to the space group P3(1)21 (or P3(2)21), with unit-cell parameters a = b = 70.38, c = 148.93 A. The asymmetric unit contains two subunits, with a corresponding V(M) of 1.90 A(3) Da(-1) and a solvent content of 35.3%.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗