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1.
PLoS Genet ; 18(9): e1010404, 2022 09.
Article in English | MEDLINE | ID: mdl-36121845

ABSTRACT

Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions.


Subject(s)
Mosaicism , Neoplasms , Gene Frequency , Humans , Mutation , Neoplasms/genetics , Exome Sequencing
2.
Sensors (Basel) ; 23(2)2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36679539

ABSTRACT

Visible light communication (VLC) has contributed new unused spectrum in addition to the traditional radio frequency communication and can play a significant role in wireless communication. The adaptation of VLC technology enhances wireless connectivity both in indoor and outdoor environments. Multiple-input multiple-output (MIMO) communication has been an efficient technique for increasing wireless communications system capacity and performance. With the advantages of MIMO techniques, VLC can achieve an additional degree of freedom. In this paper, we systematically perform a survey of the existing work based on MIMO VLC. We categorize the types of different MIMO techniques, and a brief description is given. Different problem-solving approaches are given in the subsequent sections. In addition, machine learning approaches are also discussed in sufficient detail. Finally, we identify the future study direction for MIMO-based communication in VLC.


Subject(s)
Acclimatization , Machine Learning , Information Technology , Light
3.
Sensors (Basel) ; 23(18)2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37765850

ABSTRACT

The intelligent reflecting surface (IRS) is a two-dimensional (2D) surface with a programmable structure and is composed of many arrays. The arrays are used to supervise electromagnetic wave propagation by altering the electric and magnetic properties of the 2D surface. IRS can influentially convert wireless channels to very effectively enhance spectral efficiency (SE) and communication performance in wireless systems. However, proper channel information is necessary to realize the IRS anticipated gains. The conventional technique has been taken into consideration in recent attempts to fix this issue, which is straightforward but not ideal. A deep learning model which is called the long short-term memory (Bi-LSTM) model can tackle this issue due to its good learning capability and it plays a vital role in enhancing SE. Bi-LSTM can collect data from both forward and backward directions simultaneously to provide improved prediction accuracy. Because of the tremendous benefits of the Bi-LSTM model, in this paper, an IRS-assisted Bi-LSTM model-based multi-user multiple input single output downlink system is proposed for SE improvement. A Wiener filter is used to determine the optimal phase of each IRS element. In the simulation results, the proposed system is compared with other DL models and methods for the SE performance evaluation. The model exhibits satisfactory SE performance with a different signal-to-noise ratio compared to other schemes in the online phase.

4.
Sensors (Basel) ; 19(14)2019 Jul 22.
Article in English | MEDLINE | ID: mdl-31336590

ABSTRACT

Most approaches for moving object detection (MOD) based on computer vision are limited to stationary camera environments. In advanced driver assistance systems (ADAS), however, ego-motion is added to image frames owing to the use of a moving camera. This results in mixed motion in the image frames and makes it difficult to classify target objects and background. In this paper, we propose an efficient MOD algorithm that can cope with moving camera environments. In addition, we present a hardware design and implementation results for the real-time processing of the proposed algorithm. The proposed moving object detector was designed using hardware description language (HDL) and its real-time performance was evaluated using an FPGA based test system. Experimental results demonstrate that our design achieves better detection performance than existing MOD systems. The proposed moving object detector was implemented with 13.2K logic slices, 104 DSP48s, and 163 BRAM and can support real-time processing of 30 fps at an operating frequency of 200 MHz.

5.
Diabetes Obes Metab ; 20(10): 2408-2415, 2018 10.
Article in English | MEDLINE | ID: mdl-29862619

ABSTRACT

AIM: To evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: This double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT). RESULTS: In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 µU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted. CONCLUSIONS: Ipragliflozin as add-on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucosides/administration & dosage , Metformin/administration & dosage , Sitagliptin Phosphate/administration & dosage , Thiophenes/administration & dosage , Adult , Aged , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Double-Blind Method , Drug Therapy, Combination , Female , Glucosides/adverse effects , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Male , Metformin/adverse effects , Middle Aged , Republic of Korea , Sitagliptin Phosphate/adverse effects , Thiophenes/adverse effects , Treatment Outcome , Young Adult
6.
Arch Microbiol ; 199(4): 597-603, 2017 May.
Article in English | MEDLINE | ID: mdl-28028566

ABSTRACT

A Gram-negative, aerobic, non-motile, rod-shaped bacterial strain, designated MAB-07T, was isolated from the gut of a red snow crab. The novel strain grew optimally at 20 °C, pH 7.0-8.0, and in the presence of 3% (w/v) NaCl. A phylogenetic analysis based on the 16S rRNA gene sequence indicated that the strain MAB-07T belongs to the type strains of species of the genus Lacinutrix. Strain MAB-07T exhibited 16S rRNA gene sequence similarity values of 95.5-97.8% with the type strains of species of the genus Lacinutrix. The predominant cellular fatty acids of strain MAB-07T were iso-C15:1 G (27.5%) and iso-C15:0 (21.7%). The major respiratory quinine was identified as MK-6. The polar lipids consisted of phosphatidylethanolamine, four unidentified aminolipids, and two unidentified lipids. The genomic DNA G + C content was determined to be 33.3%, and its DNA-DNA relatedness values with the type strains of L. venerupis, L. mariniflava, L. jangbogonensis, L. algicola, and Olleya aquimaris were 28-32%. Based on the data from this polyphasic taxonomic study, strain MAB-07T is considered to represent a novel species of the genus Lacinutrix, for which the name L. chionocetis sp. nov. is proposed. The type strain is MAB-07T (=KCTC 42767T = JCM 30988T).


Subject(s)
Brachyura/microbiology , Flavobacteriaceae/classification , Animals , Base Composition , DNA, Bacterial/chemistry , Fatty Acids/analysis , Flavobacteriaceae/chemistry , Flavobacteriaceae/isolation & purification , Gastrointestinal Tract/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics , Vitamin K 2/analogs & derivatives , Vitamin K 2/analysis
7.
Biomarkers ; 21(3): 243-8, 2016.
Article in English | MEDLINE | ID: mdl-26846433

ABSTRACT

Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create a substantial public health problem worldwide. To date, no therapeutic can effectively solve these problems. They are complex diseases characterized by both genetic and environmental factors. DNA methylation can act as a downstream effector of environmental signals and account for multi-factorial nature of the disease. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Alu elements host one-quarter of CpG dinucelotides in the genome to function as proxies for global DNA methylation. In this study, we evaluated the Alu methylation in the peripheral blood DNA of healthy volunteers and AUD patients using the pyrosequencing technology. The Alu methylation level is significantly higher in AUD compared to healthy controls (23.4 ± 1.6 versus 22.1 ± 1.0, t = 7.83, p < 0.0001). Moreover, significant correlation was found between Alu methylation and alcohol use disorders identification test score (r = 0.250, p < 0.0001), alcohol problem (r = 0.294, p < 0.0001), and life position (r = -0.205, p = 0.0005). Overall, these novel findings indicate that alcohol-related increase in Alu methylation might play a complex role in the etiology and pathogenesis of AUD. Further studies are required to elucidate the mechanisms underlying this relationship.


Subject(s)
Alcohol Drinking/adverse effects , Alu Elements/genetics , Biomarkers/blood , DNA Methylation/genetics , DNA/blood , Adult , Aged , Alcohol Drinking/blood , Alcohols/adverse effects , CpG Islands/genetics , DNA/genetics , Female , Humans , Male , Middle Aged
8.
Sensors (Basel) ; 16(2): 203, 2016 Feb 05.
Article in English | MEDLINE | ID: mdl-26861331

ABSTRACT

Precise time-of-arrival (TOA) estimation is one of the most important techniques in RF-based positioning systems that use wireless sensor networks (WSNs). Because the accuracy of TOA estimation is proportional to the RF signal bandwidth, using broad bandwidth is the most fundamental approach for achieving higher accuracy. Hence, ultra-wide-band (UWB) systems with a bandwidth of 500 MHz are commonly used. However, wireless systems with broad bandwidth suffer from the disadvantages of high complexity and high power consumption. Therefore, it is difficult to employ such systems in various WSN applications. In this paper, we present a precise time-of-arrival (TOA) estimation algorithm using an IEEE 802.15.4 ZigBee system with a narrow bandwidth of 2 MHz. In order to overcome the lack of bandwidth, the proposed algorithm estimates the fractional TOA within the sampling interval. Simulation results show that the proposed TOA estimation algorithm provides an accuracy of 0.5 m at a signal-to-noise ratio (SNR) of 8 dB and achieves an SNR gain of 5 dB as compared with the existing algorithm. In addition, experimental results indicate that the proposed algorithm provides accurate TOA estimation in a real indoor environment.

9.
Biomarkers ; 20(2): 136-42, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25585924

ABSTRACT

Promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) DNA repair gene is important during carcinogenesis. We explored whether organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), were associated with hypermethylation of the MGMT gene promoter in peripheral leukocytes among 368 Koreans without cancer. Hypermethylation decreased as OCPs increased (Ptrend = 0.02), while PCB concentrations showed an inverted U-shaped association (Pquadratic < 0.01). The prevalence of MGMT promoter hypermethylation was highest within the 2nd quintile of the PCB summary score (28.4%), while it was only 2.7% in the upper 10% score. Chronic exposure to these chemicals may affect methylation of the MGMT promoter, with possibly non-monotonic dose response relationships.


Subject(s)
DNA Methylation , Hydrocarbons, Chlorinated/blood , Pesticides/blood , Polychlorinated Biphenyls/blood , Case-Control Studies , Environmental Pollutants/blood , Gas Chromatography-Mass Spectrometry , Humans , Logistic Models , Middle Aged , O(6)-Methylguanine-DNA Methyltransferase/genetics , Polymerase Chain Reaction , Promoter Regions, Genetic/genetics , Surveys and Questionnaires
10.
Sensors (Basel) ; 16(1)2015 Dec 25.
Article in English | MEDLINE | ID: mdl-26712761

ABSTRACT

In the detection of moving objects from vision sources one usually assumes that the scene has been captured by stationary cameras. In case of backing up a vehicle, however, the camera mounted on the vehicle moves according to the vehicle's movement, resulting in ego-motions on the background. This results in mixed motion in the scene, and makes it difficult to distinguish between the target objects and background motions. Without further treatments on the mixed motion, traditional fixed-viewpoint object detection methods will lead to many false-positive detection results. In this paper, we suggest a procedure to be used with the traditional moving object detection methods relaxing the stationary cameras restriction, by introducing additional steps before and after the detection. We also decribe the implementation as a FPGA platform along with the algorithm. The target application of this suggestion is use with a road vehicle's rear-view camera systems.

11.
Sensors (Basel) ; 14(9): 17516-29, 2014 Sep 18.
Article in English | MEDLINE | ID: mdl-25237900

ABSTRACT

Research on real-time health systems have received great attention during recent years and the needs of high-quality personal multichannel medical signal compression for personal medical product applications are increasing. The international MPEG-4 audio lossless coding (ALS) standard supports a joint channel-coding scheme for improving compression performance of multichannel signals and it is very efficient compression method for multi-channel biosignals. However, the computational complexity of such a multichannel coding scheme is significantly greater than that of other lossless audio encoders. In this paper, we present a multichannel hardware encoder based on a low-complexity joint-coding technique and shared multiplier scheme for portable devices. A joint-coding decision method and a reference channel selection scheme are modified for a low-complexity joint coder. The proposed joint coding decision method determines the optimized joint-coding operation based on the relationship between the cross correlation of residual signals and the compression ratio. The reference channel selection is designed to select a channel for the entropy coding of the joint coding. The hardware encoder operates at a 40 MHz clock frequency and supports two-channel parallel encoding for the multichannel monitoring system. Experimental results show that the compression ratio increases by 0.06%, whereas the computational complexity decreases by 20.72% compared to the MPEG-4 ALS reference software encoder. In addition, the compression ratio increases by about 11.92%, compared to the single channel based bio-signal lossless data compressor.


Subject(s)
Biosensing Techniques , Signal Processing, Computer-Assisted , Software , Databases, Factual , Entropy , Equipment and Supplies , Humans
12.
Sensors (Basel) ; 13(5): 6775-92, 2013 May 21.
Article in English | MEDLINE | ID: mdl-23698271

ABSTRACT

A single-chip sensor system-on-a-chip (SoC) that implements radio for 2.4 GHz, complete digital baseband physical layer (PHY), 10-bit sigma-delta analog-to-digital converter and dedicated sensor calibration hardware for industrial sensing systems has been proposed and integrated in a 0.18-µm CMOS technology. The transceiver's building block includes a low-noise amplifier, mixer, channel filter, receiver signal-strength indicator, frequency synthesizer, voltage-controlled oscillator, and power amplifier. In addition, the digital building block consists of offset quadrature phase-shift keying (OQPSK) modulation, demodulation, carrier frequency offset compensation, auto-gain control, digital MAC function, sensor calibration hardware and embedded 8-bit microcontroller. The digital MAC function supports cyclic redundancy check (CRC), inter-symbol timing check, MAC frame control, and automatic retransmission. The embedded sensor signal processing block consists of calibration coefficient calculator, sensing data calibration mapper and sigma-delta analog-to-digital converter with digital decimation filter. The sensitivity of the overall receiver and the error vector magnitude (EVM) of the overall transmitter are -99 dBm and 18.14%, respectively. The proposed calibration scheme has a reduction of errors by about 45.4% compared with the improved progressive polynomial calibration (PPC) method and the maximum current consumption of the SoC is 16 mA.

13.
Asian Biomed (Res Rev News) ; 17(1): 39-42, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37706054

ABSTRACT

Background: The urine immunochromatographic assay is a useful screening tool for patients suspected of acute drug intoxication in emergency conditions. Diphenhydramine intoxication shows symptoms similar to those of tricyclic antidepressant (TCA) intoxication. Case presentation: We examined a case of diphenhydramine intoxication showing cerebellar ataxia and prolonged false positive results for TCA in the urine. The urine TCA test showed persistently positive results even 60 h after the patient's initial drug screening. We observed negative conversion 90 h after the initial drug screening. Discussion: Considering the similarities of clinical symptoms between diphenhydramine and TCA intoxication, emergency physicians should consider the possibility of cross-reactivity in the diagnosis of a patient with unknown acute drug intoxication showing positive results of TCA immunochromatographic assay in the urine. Conclusion: The present case suggests that diphenhydramine overdose may cause cerebellar ataxia and show prolonged cross-reactivity as TCA in the urine.

14.
Neurol Sci ; 33(4): 923-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22124851

ABSTRACT

We report on a 66-year-old woman with a posterior circulation stroke that occurred after bronchial artery embolization (BAE) due to post-tuberculous bronchiectasis. Stroke is a rare complication of BAE and is usually thought to be caused by inadvertent embolization via a bronchial artery-pulmonary vein shunt. However, the possibility of thromboembolic stroke should be considered, because of the patient's possible underlying anatomical variations or atherothrombosis.


Subject(s)
Bronchial Arteries/physiopathology , Embolization, Therapeutic/adverse effects , Stroke/etiology , Aged , Angiography, Digital Subtraction , Bronchial Arteries/diagnostic imaging , Bronchiectasis/etiology , Bronchiectasis/therapy , Diffusion Magnetic Resonance Imaging , Female , Humans , Magnetic Resonance Angiography , Tuberculosis/complications
15.
Sensors (Basel) ; 13(1): 375-92, 2012 Dec 27.
Article in English | MEDLINE | ID: mdl-23271602

ABSTRACT

The focus of many leading technologies in the field of medical sensor systems is on low power consumption and robust data transmission. For example, the implantable cardioverter-defibrillator (ICD), which is used to maintain the heart in a healthy state, requires a reliable wireless communication scheme with an extremely low duty-cycle, high bit rate, and energy-efficient media access protocols. Because such devices must be sustained for over 5 years without access to battery replacement, they must be designed to have extremely low power consumption in sleep mode. Here, an on-time, energy-efficient scheduling scheme is proposed that performs power adjustments to minimize the sleep-mode current. The novelty of this scheduler is that it increases the determinacy of power adjustment and the predictability of scheduling by employing non-pre-emptible dual priority scheduling. This predictable scheduling also guarantees the punctuality of important periodic tasks based on their serialization, by using their worst case execution time) and the power consumption optimization. The scheduler was embedded into a system on chip (SoC) developed to support the wireless body area network-a wakeup-radio and wakeup-timer for implantable medical devices. This scheduling system is validated by the experimental results of its performance when used with life-time extensions of ICD devices.

16.
Mol Carcinog ; 49(10): 913-21, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20721975

ABSTRACT

Based on the important role of microRNA (miRNA) biosynthesis genes in carcinogenesis, we hypothesized that polymorphisms in the miRNA biosynthesis genes may modulate susceptibility to lung cancer. To test this hypothesis, we conducted a two-stage study to evaluate the associations between single nucleotide polymorphisms (SNPs) in the miRNA biosynthesis genes and the risk of lung cancer. In stage 1 of the study, 24 SNPs in the 11 miRNA biosynthesis genes (DROSHA, DGCR8, RAN, XPO5, DICER, AGO1, AGO2, HIWI, GEMIN3, GEMIN4, and TRBP) were genotyped in 100 lung cancer patients and 100 healthy controls using a sequenome mass spectrometry-based genotyping assay. One promising SNP (AGO1 rs636832A > G) was selected for stage 2 of the study, and genotyped by a melting-curve analysis using fluorescence-labeled hybridization probes in an independent set of 552 cases and 552 controls. The AGO1 rs636832A > G exhibited highly consistent results between the two stages of the study. In combined analysis, the 636832A > G was associated with a significantly decreased risk of lung cancer in a dose-dependent manner (P(trend) = 6.0 × 10(-4)). Individuals with at least one rs636832G allele were at a significantly decreased risk of lung cancer compared with those with the AA genotype (adjusted odds ratio = 0.67, 95% confidence interval = 0.53-0.84, P = 4.0 × 10(-4)). This finding suggests that the AGO1 rs636832A > G might be a useful marker for determining the susceptibility to lung cancer and that the AGO1 gene might be involved in the development of lung cancer.


Subject(s)
Eukaryotic Initiation Factors/genetics , Lung Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Aged , Argonaute Proteins , Case-Control Studies , Female , Genotype , Humans , Male , Middle Aged , Risk , Smoking
17.
Technol Health Care ; 28(S1): 487-497, 2020.
Article in English | MEDLINE | ID: mdl-32364181

ABSTRACT

BACKGROUND: Biomedical engineers in particular require fast and powerful data processing systems to process computerized tomography and magnetic resonance imaging scans and other medical imaging technologies. However, current computer data processing technologies are unable to satisfy such requirements. A promising approach to addressing these limitations is processing in memory (PIM). Unfortunately, several issues, such as the compatibility and interconnection of PIM with legacy systems, still remain. OBJECTIVE: This paper proposes a standard memory bus-based PIM interface for medical image processing and a PIM platform. The proposed PIM interface can overcome problems of compatibility with legacy systems. METHODS: We will adapt an embedded system based on a commercial application processor (AP) to a medical image system to verify the functions and the performance of the proposed PIM interface. Using the PIM platform, we apply the proposed PIM interface and the AP to execute an image processing program, measure the image processing times, and compare the results of the measurements. RESULTS: Experimental results show that while the functions of the proposed PIM interface are normal, the processing time of PIM is more than 81% faster than that of the AP. CONCLUSION: The experimental results prove that the proposed PIM interface is able to solve problems of compatibility with legacy systems. We foresee that not only the medical image processing field but also a number of academic fields and professional sectors will use PIM in their data-intensive applications.


Subject(s)
Electronic Data Processing/methods , Image Processing, Computer-Assisted/methods , Humans , Time Factors
18.
Mol Carcinog ; 48(12): 1109-15, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19554572

ABSTRACT

Promoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation-specific PCR (MSP) and correlated the methylation status with clinicopathological features. With standard MSP analysis, HOXA5 methylation were found in 113 (81.3%) of 139 NSCLCs and 72 (51.8%) in their corresponding nonmalignant lung tissues. RT-PCR and immunohistochemical analysis showed that HOXA5 methylation correlates with gene expression. Moreover, in the patients with stage I disease, HOXA5 methylation was more frequent in smokers than in never-smokes (P = 0.01). There was no influence of HOXA5 methylation on survival in all NSCLCs or at stages II-IV. However, in the patients with stage I disease, HOXA5 methylation was associated with a borderline significantly worse survival (P = 0.09). These findings suggest that downregulation of the HOXA5 gene by aberrant promoter methylation occurs in the vast majority of NSCLCs and that it may play a role in the pathogenesis of NSCLC. Additional studies with larger sample sizes are required to evaluate the prognostic value of HOXA5 methylation in patients with stage I NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Lung Neoplasms/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/secondary , Female , Humans , Immunoenzyme Techniques , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate
19.
Clin Ther ; 31(5): 1037-45, 2009 May.
Article in English | MEDLINE | ID: mdl-19539104

ABSTRACT

BACKGROUND: Alendronate sodium is a Bisphosphonate drug used to treat and prevent osteoporosis and several other bone diseases. A new formulation has been developed and is currently awaiting regulatory approval, pending findings on bioequivalence. OBJECTIVES: The aims of the present study were to compare the bioavailability and pharmacokinetic (PK) properties, and to determine the bioequivalence, of a test and reference formulation of alendronate sodium 70 mg in a healthy Korean adult male population. METHODS: This open-label, randomized, 2-sequence, 2-period crossover study was carried out at Hanyang University Medical Center (Seoul, Republic of Korea). Healthy Korean adult male volunteers were randomly assigned to receive a single 70-mg dose of the test or reference formulation of alendronate sodium, administered with 240 mL of water, followed by a 7-day washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Serial blood samples were collected and adverse events were monitored by a clinical investigator via observation, personal interview, and vital signs (blood pressure, heart rate, and body temperature) over a 7-hour period (at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, and 7 hours) after drug administration. Plasma alendronate sodium concentrations were determined using a validated high-performance liquid chromatographic-postcolumn fluorescence derivatization method, with visible detection in the range of 2 to 100 ng/mL and lower limit of quantification set at 2 ng/mL. PK properties, including AUC(0-t), AUC(0-infinity), C(max), T(max), t(1/2), and the elimination constant (k(e)), were determined using non-compartmental analysis. The formulations were considered bioequivalent if the 90% CI ratios for C(max) and AUC were within the predetermined interval of 80% to 125%, the regulatory definition set by the US Food and Drug Administration (FDA). RESULTS: Twenty-three healthy male volunteers (mean [SD] age, 23.5 [2.0] years [range, 19-28 years]; height, 175.9 [5.4] cm [range, 162.0-185.0 cm]; and weight, 71.2 [9.5] kg [range, 61-96 kg]) were included in the study. No period or sequence effects were detected. The 90% CIs for the corresponding ratios of AUC(0-t), AUC(0-infinity) and C(max) were 84.97 to 114.47, 86.09 to 115.59, and 82.37 to 110.71, respectively. Additionally, the mean (range) of T(max) was 1.09 hours (0.5-2.0 hours), and the mean (SD) of t(1/2) and k(e) were 2.04 (0.97) hours and 0.34 (0.71) hour, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition interval of 80% to 125%. No adverse events were reported in this study. CONCLUSIONS: Single doses of these formulations of alendronate sodium 70 mg met the criteria for bio-equivalence. No statistically significant differences in AUC(0-t), AUC(0-infinity), and C(max) were found in this healthy Korean adult male population.


Subject(s)
Alendronate/administration & dosage , Alendronate/pharmacokinetics , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/pharmacokinetics , Administration, Oral , Adult , Alendronate/blood , Area Under Curve , Biological Availability , Bone Density Conservation Agents/blood , Chromatography, Liquid , Cross-Over Studies , Drug Administration Schedule , Humans , Korea , Male , Reference Values , Therapeutic Equivalency , Young Adult
20.
Endocr J ; 56(1): 141-7, 2009.
Article in English | MEDLINE | ID: mdl-18997443

ABSTRACT

GH plays an important role in lipid metabolism as a partitioning hormone. PPARdelta regulates lipid oxidation in skeletal muscle and is activated by several physiological ligands including fatty acids. To investigate whether GH has an effect on the regulation of transcription of PPARdelta and other genes involved in energy metabolism in skeletal muscle, mRNA levels were studied by real-time RT-PCR in lit/lit mice (isolated GH deficiency) and lit/+ mice controls (normal GH levels). Mice received either a single bolus (120 ng/g) of rat GH or vehicle, and skeletal muscle was collected 4h later. PPARdelta mRNA was increased in vehicle-treated lit/lit mice compared to vehicle-treated lit/+ mice (1.67 fold, P<0.05). lit/lit mice treated with GH showed a further increase in PPARdelta mRNA levels (2.83 fold vs. vehicle-treated lit/+ mice, P<0.001). mRNA levels of Foxo1 were increased in vehicle-treated lit/lit mice compared to vehicle-treated lit/+ mice (1.74 fold, P<0.05). lit/lit mice treated with GH showed a further increase in Foxo1 mRNA levels (6.30 fold vs. vehicle-treated lit/+ mice, P<0.001). mRNA levels of acyl CoA-oxidase showed a trend to be higher in vehicle-treated lit/lit mice compared to vehicle-treated lit/+ mice. This reached statistical significance in GH-treated lit/lit mice compared to vehicle-treated lit/+ mice (2.11 fold, P<0.05). In summary, mRNA levels of PPARdelta and Foxo1 were increased in skeletal muscle of GH-deficient mice, and further acutely increased by GH administration. These results suggest that GH plays a relevant role in the lipid catabolism in skeletal muscle.


Subject(s)
Dwarfism, Pituitary/genetics , Forkhead Transcription Factors/genetics , Growth Hormone/pharmacology , Muscle, Skeletal/drug effects , PPAR delta/genetics , Acyl-CoA Oxidase/genetics , Acyl-CoA Oxidase/metabolism , Animals , Body Weight/drug effects , Dwarfism, Pituitary/metabolism , Dwarfism, Pituitary/pathology , Forkhead Box Protein O1 , Forkhead Transcription Factors/metabolism , Homozygote , Insulin/blood , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Muscle, Skeletal/metabolism , PPAR alpha/genetics , PPAR alpha/metabolism , PPAR delta/metabolism , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Up-Regulation/drug effects
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