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Biomedical subjects

Hee Chan Kim

Publications and source records attributed to Hee Chan Kim.

At least 19 recordsLinked to original sources

Application of high throughput cell array technology to FISH: investigation of the role of deletion of p16 gene in leukemias.

Bio-cell chip is a chip that has hundreds of types of cells arrayed and immobilized on a small slide. To elucidate the role of deletion of the p16 gene in hematologic malignancies, the bio-cell chip technique was applied to fluorescent in situ hybridization (FISH) study. We made a bio-cell chip with bone marrow specimen from 109 patients with acute lymphoblastic leukemia (ALL), 102 patients with acute myelogenous leukemia (AML), 47 patients with chronic myelogenous leukemia (CML), and 25 patients with multiple myeloma (MM). A glass slide with 96 separated areas was fabricated, onto which was added methanol/acetic acid fixed cell suspensions for high-throughput FISH for p16. With the successful application of bio-cell chip technique, we found that the deletion of p16 contributed to the oncogenesis in acute leukemia, but not in chronic leukemia. In conclusion, the bio-cell chip, a cell version of ultrahigh-throughput technology, was successfully applied to the FISH study, which can be utilized efficiently in the molecular cytogenetic investigation of hematologic malignancies.

Acute Disease↗

Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma.

The most frequent genetic aberrations in multiple myeloma (MM) are 13q deletions and translocations involving the immunoglobulin heavy chain gene (IGH). There have been no reports on the cytogenetic abnormalities found in Korean patients with MM. We investigated the actual prevalence and prognostic value of cytogenetic changes using fluorescence in situ hybridization (FISH). FISH studies with 12 different specific probes for the regions containing the genes or chromosome regions (13q, 1q, IGH, p53, MLL, p16, CEP 7, CEP 11, and CEP 12) were performed in 128 patients. The most frequent change found was 13q deletion (48%), followed by trisomy 1q (45%), IGH translocation (37%), and trisomy 11 (26%). Among the three different probes used to detect 13q deletion, D13S25 (48/58) was the most sensitive probe compared to RB (43/58) and D13S319 (39/58). Among the patients showing one or more changes by FISH, 75% (82/110) had a 13q deletion, a trisomy 1q, or an IGH translocation. Azotemia, anemia, thrombocytopenia, intramedullary plasmacytosis, and stage were significantly associated with the 13q deletion; serum beta(2)-microglobulin, thrombocytopenia, and intramedullary plasmacytosis were also related to trisomy 1q. The pattern of molecular cytogenetic changes in Korean patients with MM is somewhat different from what has been observed in reported Caucasian populations: 37 versus 50-70% with regard to the IGH translocation. The prevalence of the 13q deletion was similar in Korean and Caucasian populations, 48 versus 30-50%. We suggest that the detection of at least these three genetic changes, 13q- trisomy 1q, and an IGH rearrangement, would be helpful for follow-up of Korean patients with MM.

Adult↗

Deletion of any part of the BCR or ABL gene on the derivative chromosome 9 is a poor prognostic marker in chronic myelogenous leukemia.

To evaluate the prognostic significance of submicroscopic deletions of the ABL or BCR gene associated with t(9;22) in chronic myelogenous leukemia (CML), we investigated the incidence of an ABL or BCR deletion on derivative chromosome 9 using fluorescence in situ hybridization (FISH). FISH was performed using the LSI BCR/ABL dual-fusion translocation probe on bone marrow cells of 86 patients with CML. Of 86 patients, ABL deletion was detected in 13 (15.1%) patients and BCR deletion in 8 patients (9.3%). Patients with ABL deletion showed shorter event-free survival time (EFS) than those without ABL deletion (P = 0.020). Patients with BCR deletion showed significantly short overall survival time (OS; P = 0.039). Patients with ABL and/or BCR deletion (14/86 patients, 16.3%) showed significantly short OS and EFS (median OS, 43.0 months; median EFS, 40.0 months), compared to the patients without any BCR or ABL gene deletions (median OS, 94.0 months; median EFS, 90.0 months; P = 0.041 for OS, P = 0.008 for EFS). All the patients with BCR deletion, except for one, had a concomitant ABL deletion, suggesting that BCR deletion occurs in conjunction with ABL deletion. In patients with ABL deletion only, BCR/ABL rearrangement with b2a2 mRNA type tended to be more frequent than in patients without any deletion of the two genes (P = 0.073). Deletion of any of the BCR or ABL genes on derivative chromosome 9 was associated with both short OS and EFS. We conclude that deletion of not only the ABL gene, but also of the BCR gene, is a poor prognostic marker that indicates rapid disease progression in CML.

Acute Disease↗

Electrochemical nanoneedle biosensor based on multiwall carbon nanotube.

We report the fabrication and analytical functions of a biosensor based on a nanoneedle consisting of a multiwall carbon nanotube attached to the end of an etched tungsten tip. The devised electrode is the smallest needle-type biosensor reported to date. The nanoneedles prepared in this work are 30 nm in diameter and 2-3 microm in length. Dopamine and glutamate, which are physiologically important neurotransmitters, were successfully detected using these nanoneedles. Bare nanoneedles detected dopamine in the range from 100 to 1000 microM by differential pulse voltammetry, and enzyme-modified nanoneedles were able to respond to glutamate in the 100-500 microM range by potentiostatic amperometry.

Biosensing Techniques↗

Preliminary evaluation of the use of a CDMA-based emergency telemedicine system.

We have conducted a preliminary evaluation of the use of a code division multiple access (CDMA)-based emergency telemedicine system to be used by emergency rescuers providing first-aid treatment for patients. The prototype system included five instrumentation modules for measuring non-invasive arterial blood pressure (NIBP), arterial oxygen saturation (SpO(2)), six-channel electrocardiogram (ECG), blood glucose concentration and body temperature. The patient data were transferred to a doctor's PC through CDMA and TCP/IP networks using an embedded personal digital assistant (PDA) phone. Performance tests in the laboratory showed that the system provided reliable values with error ranges within +/-1% for heart rate, +/-5 mmHg for NIBP, +/-2% for SpO(2) and +/-1% for glucose. The feasibility of the prototype system was then evaluated with 15 real emergency patients on Jeju Island over a two-month period. Measured data were transmitted from a moving ambulance to the emergency medical centre without significant CDMA connection loss or transmission errors. The average transfer time was 8 min. Four emergency doctors and 11 rescuers completed a questionnaire. There were favourable reviews from the users.

Cell Phone↗

pH-sensitive solid-state electrode based on electrodeposited nanoporous platinum.

The nanoporous platinum oxide (H1-ePtO) as a hydrogen ion-selective sensing material is reported. Bare nanoporous platinum oxides exhibit near-Nernstian behavior (e.g., -55 mV/pH in PBS), ignorable hysteresis, a short response time, and high precision, which are remarkably better than those of flat platinum oxides. The electrode potential of a nanoporous platinum oxide responds exclusively to hydrogen ion, which implies its usefulness as a solid-state pH sensor. In the present study, the performance of nanoporous platinum oxide was investigated and compared with that of IrOx in terms of selectivity and the influences of ionic strength, temperature, complexing ligands, and surfactants. H1-ePtO functions well as a pH-sensing solid-state material, and it is viewed as a promising alternative to IrOx. Interference by redox couples was successfully suppressed by covering the H1-ePtO surface with a protective layer, e.g., an electropolymerized polyphenol thin film. Since the nanoporous platinum oxide with such a protective layer is particularly suitable for miniaturization and micropatterning, our findings suggest its usefulness in applications such as solid-state pH sensors embedded in chip-based microanalysis systems.

Cations↗

Korean patients with chronic lymphocytic leukemia show the similar types of chromosomal aberrations as those in Europe and North America.

Chronic lymphocytic leukemia (CLL) is frequent in the West, but rare in Korea. In this study, the frequency of chromosome aberration in Korean CLL patients was examined by applying interphase fluorescence in situ hybridization (FISH). Conventional cytogenetic test and FISH were performed on bone marrow aspirates obtained from 16 CLL patients. By applying DNA probes (Vysis, Downers Grove, IL, USA), the deletion in 11q22-23, 13q14, 13q34, and 17p13, and trisomy 12 were examined. With FISH, molecular cytogenetic aberration was detected in 10 of 16 patients [63%, 95% confidence interval (CI) 39-86], whereas with conventional cytogenetic test, chromosomal aberration was detected only in 2 out of 13 cases (15%, 95% CI 0-35). In total, the cases with one or more chromosomal aberrations were 11 out of 16 cases (69%, 95% CI 46-92). The most frequently detected aberration was the 13q14 deletion (69%, 95% CI 44-94), followed by trisomy 12 (19%, 95% CI 0-38) and 11q22 deletion (14%, 95% CI 0-33). No deletion in 17p13 was observed. In conclusion, CLL in Korean is a heterogeneous genetic disorder, showing similar genetic changes in Europe and North America.

Aged↗

Cytometry and velocimetry on a microfluidic chip using polyelectrolytic salt bridges.

This paper reports a polyelectrolytic salt bridge-based electrode (PSBE), which is a key embedded unit in a microchip device that can size-selectively count microparticles and measure their velocities. The construction of salt bridges at specific locations within a microfluidic chip enables dc-driven electrical detection to be performed successfully. This is expected to be a competitive alternative to the optical methods currently used in conventional cell sorters. The PSBEs were fabricated by irradiating ultraviolet light over a patterned mask on the parts of interest, which were filled with an aqueous monomer solution containing diallyldimethylammonium chloride. A pair of such PSBEs was easily formed at the two lateral branches perpendicular to the main microchannel and was found to be very useful for dc impedometry. The human blood cells as well as the fluorescent microbeads passing between the two PSBEs produced impedance signals in proportional to their size. The information about the velocity of a microparticle was extracted from a doublet of the dc impedance signals, which were generated when cells or microbeads sequentially passed through two PSBE pairs separated from each other by a fixed distance. The plot of peak amplitude versus velocity of the moving microbeads and cells indicated only a slight correlation between the size and the velocity, which means that the peak amplitude of the dc impedance signals alone can provide information about the size of the cells in a mixture. The experimental results showed a screening rate of over 1000 cells s(-1) and a velocity of the cells of over 100 mm s(-1). Compared with the previously suggested electrical detection system based on metal electrodes, the sensitivity and selectivity in cell detection were remarkably improved. In addition, the detection unit including the operating circuit became innovatively simple and the whole device could be miniaturized.

Blood Cell Count↗

Interpretation of submicroscopic deletions of the BCR or ABL gene should not depend on extra signal-FISH: problems in interpretation of submicroscopic deletion of the BCR or ABL gene with extra signal-FISH.

Several groups have demonstrated that a submicroscopic gene deletion in Ph+ chronic myelogenous leukemia (CML) is associated with a poor prognosis and reduced response to treatment. To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion, we performed an extra signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative myeloproliferative disorder as determined by RT-PCR. The normal cutoff values were 0.22% for ES-FISH and 0.25% for D-FISH. The cutoff values for false-positive signals from a juxtaposition of the BCR and ABL gene were 11% in ES-FISH and 13% in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the 79 patients (15.8%), and the main causes of a discrepancy were a false-positive ABL deletion (4 of 12, 33%), a variant Philadelphia chromosome (3 of 12, 25%), an inversion of derivative chromosome 9 at the very breakpoint of the ABL gene (9q32) (1 of 12, 8.3%), a cryptic variant Ph chromosome (1 of 12, 8.3%), and a marker chromosome (1 of 12, 8.3%). Although there was no significant difference in the sensitivity for the detection of the fusion signal between ES- and D-FISH, ES-FISH showed a high percentage of cells with false-positive fusion signals (1 orange, 1 green, 1 yellow), which makes it difficult to interpret the submicroscopic ABL deletion. In conclusion, an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.

Bone Marrow↗

IT-based diagnostic instrumentation systems for personalized healthcare services.

This paper describes recent research and development activities on the diagnostic instruments for personalized healthcare services in Seoul National University. Utilizing the state-of-the-art information technologies (IT), various diagnostic medical instruments have been integrated into a personal wearable device and a home telehealthcare system. We developed a wrist-worn integrated health monitoring device (WIHMD) which performs the measurements of non-invasive blood pressure (NIBP), pulse oximetry (SpO2), electrocardiogram (ECG), respiration rate, heart rate, and body surface temperature and the detection of falls to determine the onset of emergency situation. The WIHMD also analyzes the acquired bio-signals and transmits the resultant data to a healthcare service center through a commercial cellular phone. Two different kinds of IT-based blood glucometer have been developed using a cellular phone and PDA(personal digital assistant) as a main unit. A blood glucometer was also integrated within a wrist pressure measurement module which is interfaced with a cellular phone via Telecommunications Technology Association (TTA) standard in order to provide users with easiness in measuring and handling two important health parameters. Non-intrusive bio-signal measurement systems were developed for the ease of home use. One can measure his ECG on a bed while he is sleeping; measure his ECG, body temperature, bodyfat ratio and weight on a toilet seat; measure his ECG on a chair; and estimate the degree of activity by motion analysis using a camera. Another integrated diagnostic system for home telehealthcare services has been developed to include a 12 channels ECG, a pressure meter for NIBP, a blood glucometer, a bodyfat meter and a spirometer. It is an expert system to analyze the measured health data and based on the diagnostic result, the system provides an appropriate medical consultation. The measured data can be either stored on the system or transmitted to the central server through the internet. We have installed the developed systems on a model house for the performance evaluation and confirmed the possibility of the system as an effective tool for the personalized healthcare services.

Accidental Falls↗

Ionic strength-controlled virtual area of mesoporous platinum electrode.

Mesoporous electrodes provide an unusual opportunity to observe the dramatic transition of the electrochemical potential distribution in vicinity to mesoporous surfaces as the ionic strength varies. The experimental results were in accordance with what the classical Gouy-Chapman theory predicts on the basis of the correlation between Debye length (kappa-1) and the diameter of mesopores. Using the phenomenon that the electrochemically effective area of mesoporous electrode depends on the ionic strength, the faradaic current density of dioxygen reduction could be controlled by the electrolyte concentration.

Journal Article↗

Electrical behavior of polymer hydrogel composed of poly(vinyl alcohol)-hyaluronic acid in solution.

Interpenetrating polymer networks (IPN), as polymer hydrogels composed of poly(vinyl alcohol) (PVA) and hyaluronic acid (HA), which exhibited electrical sensitive behavior were prepared. The swelling behavior of the IPN/HA IPN was studied by immersing the gel in various concentrations of aqueous NaCl solutions and various pH buffer solutions. The response of the PVA/HA IPN to electric fields stimuli was also investigated. When swollen IPN was placed between a pair of electrodes, and an electric field applied, it exhibited bending behavior. The PVA/HA IPN also displayed stepwise bending behavior, depending on the magnitude of the electric stimulus. Also, for use in biosensors application, their bending behavior was studied in Hank's solution at pH 7.4.

Biocompatible Materials↗

Novel algorithm for improving accuracy of ultrasound measurement of residual urine volume according to bladder shape.

OBJECTIVES: To suggest a novel algorithm based on individually determined proportionality constants to improve the accuracy of noninvasively calculated residual urine volume using ultrasound bladder images. METHODS: The residual urine volume of 116 subjects was calculated from ultrasound images obtained using a conventional two-dimensional ultrasound device at two institutions. The proposed method uses individually determined proportionality constants for specific bladder shapes. The corresponding true residual volumes were determined by measuring the catheterized volume. The accuracy of our method was confirmed by comparing the mean and standard deviation of the fractional absolute error (FAE) versus true volume with values obtained using other methods, which rely on fixed constants. RESULTS: The calculated residual bladder volume of 116 patients correlated significantly (r = 0.94, P <0.001) and the differences from the true values were not statistically significant (P = 0.42). The mean FAE was 0.17 +/- 0.10. Subgroups divided by sex, postvoid residual urine volume (over and under 150 mL), and institution produced different results (mean FAE for men 0.15 +/- 0.11 and for women 0.18 +/- 0.12; mean FAE for greater than 150 mL, 0.16 +/- 0.11 and for less than 150 mL, 0.17 +/- 0.14; mean FAE for Seoul National University Hospital 0.15 +/- 0.10 and for Seoul National University Bundang Hospital 0.18 +/- 0.18). Our method provided better accuracy than other known formulas using a conventional two-dimensional ultrasound scanner. The latter multiply the product of the sagittal height and depth and transverse width by a fixed coefficient. CONCLUSIONS: Our method, based on individually determined proportionality constants, improved the accuracy of residual bladder volume determinations. The proposed algorithm can easily be implemented on a personal computer connected to a conventional ultrasound imaging unit.

Adult↗

Computer-aided diagnosis of solid breast nodules: use of an artificial neural network based on multiple sonographic features.

A computer-aided diagnosis (CAD) algorithm identifying breast nodule malignancy using multiple ultrasonography (US) features and artificial neural network (ANN) classifier was developed from a database of 584 histologically confirmed cases containing 300 benign and 284 malignant breast nodules. The features determining whether a breast nodule is benign or malignant were extracted from US images through digital image processing with a relatively simple segmentation algorithm applied to the manually preselected region of interest. An ANN then distinguished malignant nodules in US images based on five morphological features representing the shape, edge characteristics, and darkness of a nodule. The structure of ANN was selected using k-fold cross-validation method with k = 10. The ANN trained with randomly selected half of breast nodule images showed the normalized area under the receiver operating characteristic curve of 0.95. With the trained ANN, 53.3% of biopsies on benign nodules can be avoided with 99.3% sensitivity. Performance of the developed classifier was reexamined with new US mass images in the generalized patient population of total 266 (167 benign and 99 malignant) cases. The developed CAD algorithm has the potential to increase the specificity of US for characterization of breast lesions.

Adolescent↗

Glucose sensor based on glucose oxidase immobilized by zirconium phosphate.

Amperometric glucose sensors were fabricated using glucose oxidase (GOx) entrapped in zirconium hydrogenphosphate (ZrP), and their performance was evaluated. Reportedly, alpha-ZrP is one of the candidates that are expected to improve the stability of enzymes immobilized on solid surfaces. We intercalated GOxs into ZrP (GOx/ZrP), cast the GOx/ZrP suspension in polyvinylalcohol on a platinum electrode, and dried it in a vacuum oven. The morphological layered structure was investigated by scanning electron microscopy. The enzymatic activities, which were determined by open-circuit potentiometric technique, reached the highest when GOxs were immobilized in ZrP at ca. pH 5. In vitro tests showed good linear responses in the 0-25 mM range and the sensitivity of 0.14 nA mM(-1) at 0.4 V vs. Ag/AgCl. The sensors, as made, were stable for more than 3 days within a limited deterioration.

Biosensing Techniques↗

In vivo calibration of the subcutaneous amperometric glucose sensors using a non-enzyme electrode.

A new two-point calibration method for the subcutaneous amperometric continuous glucose sensor is reported. The proposed method is based on direct measurement of the background current (I(o)) using a non-enzyme electrode. For in vivo test, three electrodes were implanted in rabbits. Two of the three were identical needle-type enzyme electrodes with perfluorinated polymer outer layers (Pt/enzyme layer/Kel-F/PTFE/Kel-F/Nafion) that were placed in subcutaneous tissue and in a vessel (ear artery), respectively. And one non-enzyme electrode with exactly the same membrane composition as those of other two was in the subcutaneous layer to measure the background current. Implantation in the subcutaneous layer generated many crevices on the protecting layers of the electrodes. The signals from enzyme electrodes were effectively corrected by the measured background current from the non-enzyme electrode. In addition, a telemetric monitoring system was developed and evaluated for in vivo continuous glucose monitoring in order to alleviate the problems of motion artifact.

Algorithms↗

Nonenzymatic glucose detection using mesoporous platinum.

Roughness of nanoscopic dimensions can be used to selectively enhance the faradaic current of a sluggish reaction. Using this principle, we constructed mesoporous structures on the surfaces of pure platinum electrodes responding even more sensitively to glucose than to common interfering species, such as L-ascorbic acid and 4-acetamidophenol. Good sensitivities, as high as 9.6 microA cm(-2) mM(-1), were reproducibly observed in the presence of high concentration of chloride ion. The selectivities, sensitivities, and stabilities determined experimentally have demonstrated the potential of mesoporous platinum as a novel candidate for nonenzymatic glucose sensors.

Biosensing Techniques↗