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D Kang

Publications and source records attributed to D Kang.

At least 19 recordsLinked to original sources
PubMed2024

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Humans↗
PubMed2006

Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

Asian People↗
PubMed2006

SULT1E1 genetic polymorphisms modified the association between phytoestrogen consumption and bone mineral density in healthy Korean women.

Sulfotransferase 1E1 (SULT1E1) catalyze estrogen into sulfate conjugation and is involved in the metabolism of phytoestrogen. A community-based cross-sectional study was conducted on 397 Korean women, to evaluate the association between genetic polymorphisms of SULT1E1 and bone mineral density (BMD) and the combined effect of the genetic polymorphism and phytoestrogen intake for BMD in Korean women. BMDs of the distal radius and the calcaneus were measured by dual-energy X-ray absorptiometry. Genotypes of SULT1E1 IVS1-447 C>A, IVS4-1653 T>C, and *959 G>A were determined by the 5'-nuclease assay (TaqMan). Phytoestrogen intake was estimated by a food-frequency questionnaire validated against multiple 24-hour recalls. Women with the SULT1E1 *959 GG genotype had a 4.5% lower BMD at the distal radius (P (trend )= 0.05) and a 7.9% lower BMD at the calcaneus compared to those with AA genotype (P (trend) < 0.01), whereas the SULT1E1 IVS1-447 CC genotype and IVS4-1653 TT genotype were not associated with BMD. There was no significant trend of BMD with the numbers of CTG-containing haplotypes, but calcaneal BMDs significantly differed between SULT1E1 CTA-CTA haplotype and CTG-CCA haplotype (P < 0.05). When stratified by SULT1E1 genotype, the correlation between phytoestrogen consumption and BMD at the calcaneus was noteworthy in women with SULT1E1 *959 GG genotype (r = 0.25, P = 0.01) or SULT1E1 IVS 4-1653 TT genotype (r = 0.15, P = 0.02). This trend remained significant only in postmenopausal women (r = 0.36, P = 0.01) after multiple testing was corrected by the false discovery rate method. In conclusion, the genetic polymorphism of SULT1E1 *959 G > A was associated with BMD at the distal radius and calcaneus, and the association between phytoestrogen consumption and calcaneal BMD might be modified by this genetic polymorphism.

Absorptiometry, Photon↗
PubMed2006

Single-nucleotide polymorphisms and haplotypes of bone morphogenetic protein genes and peripheral bone mineral density in young Korean men and women.

Bone morphogenetic proteins (BMPs) play critical roles in osteoblast differentiation. To investigate the association between common single-nucleotide polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional study was conducted in healthy Korean men (n = 237) and women (n = 276) aged 20-39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray absorptiometry. SNPs of BMP2 (-1103C > A, c.584G > A, IVS1-2744A > G, c.893T > A), BMP4 (c.712T > C, IVS1-160C > T), and BMP6 (c.1283C > G, IVS4-6838A > G, IVS5 + 24C > T) were determined using the 5'-nuclease assay. Significant associations were observed between BMP2 c.584G > A, c.893T > A genotypes and male calcaneus as well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16% higher BMD at the calcaneus (P for trend = 0.014), whereas women with this genotype had a 7% lower BMD at the distal radius than the other genotypes (P for trend = 0.010). A significant association was also observed between BMP4 IVS1-160C > T and male calcaneus BMD (P for trend = 0.024). When the association between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was significantly associated with low bone mass in female distal radius (P for trend = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are associated with peripheral BMD in Korean men and women. However, this association is dependent on anatomical sites and gender. Thus, larger studies with complete coverage of SNPs are needed in the future.

Absorptiometry, Photon↗
PubMed2006

MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

We previously reported that 8-oxoguanine (8-oxoG) accumulates in the cytoplasm of dopamine neurons in the substantia nigra of patients with Parkinson's disease and the expression of MTH1 carrying an oxidized purine nucleoside triphosphatase activity increases in these neurons, thus suggesting that oxidative damage in nucleic acids is involved in dopamine neuron loss. In the present study, we found that levels of 8-oxoG in cellular DNA and RNA increased in the mouse nigrostriatal system during the tyrosine hydroxylase (TH)-positive dopamine neuron loss induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MTH1-null mice exhibited a greater accumulation of 8-oxoG in mitochondrial DNA accompanied by a more significant decrease in TH and dopamine transporter immunoreactivities in the striatum after MPTP administration, than in wild-type mice. We thus demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women.

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Adult↗
PubMed2005

First measurement of the transverse spin asymmetries of the deuteron in semi-inclusive deep inelastic scattering.

First measurements of the Collins and Sivers asymmetries of charged hadrons produced in deep-inelastic scattering of muons on a transversely polarized 6LiD target are presented. The data were taken in 2002 with the COMPASS spectrometer using the muon beam of the CERN SPS at 160 GeV/c. The Collins asymmetry turns out to be compatible with zero, as does the measured Sivers asymmetry within the present statistical errors.

Journal Article↗
PubMed2005

First results from the CERN axion solar telescope.

Hypothetical axionlike particles with a two-photon interaction would be produced in the sun by the Primakoff process. In a laboratory magnetic field ("axion helioscope"), they would be transformed into x-rays with energies of a few keV. Using a decommissioned Large Hadron Collider test magnet, the CERN Axion Solar Telescope ran for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling g(agamma)<1.16x10(-10) GeV-1 at 95% C.L. for m(a) less, similar 0.02 eV. This limit, assumption-free, is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment over a broad range of axion masses.

Journal Article↗
PubMed2005

Detection of the steroidogenic acute regulatory protein, StAR, in human liver cells.

Overexpressing StAR (a mitochondrial cholesterol transporter) increases (>5-fold) the rate of 27-hydroxylation of cholesterol and the rates of bile acid synthesis in primary rat hepatocytes; suggesting that the transport of cholesterol into mitochondria is rate-limiting for bile acid biosynthesis via the CYP27A1 initiated 'acidic' pathway. Our objective was to determine the level of StAR expression in human liver and whether changes in StAR would correlate with changes in CYP27A1 activity/bile acid synthesis rates in human liver tissues. StAR mRNA and protein were detected in primary human hepatocytes and HepG2 cells by RT-PCR/Northern analysis and by Western analysis, respectively. In immunocompetition assays, liver StAR was competed away with the addition of purified human adrenal StAR. Overexpressing CYP27A1 in both cell types led to >2-fold increases in liver StAR concentration. StAR protein levels also increased approximately 2-fold with the addition of 27-hydroxycholesterol to HepG2 cell culture medium. Overexpressing StAR increased the rates of 27-hydroxylation of cholesterol/bile acid synthesis in both cell lines and increased intracellular levels of 27-hydroxycholesterol. In conclusion, human liver cells contain regulable StAR protein whose level of expression appears capable of regulating cellular cholesterol homeostasis, representing a potential therapeutic target in the management of hyperlipidemia.

Bile Acids and Salts↗
PubMed2005

Trigemino-cervical response in patients with amyotrophic lateral sclerosis.

PURPOSE: The trigemino-cervical response (TCR) was investigated in the patients with amyotrophic lateral sclerosis (ALS) to evaluate its effect for disclosing the bulbar involvement in this disorder. METHODS: We studied 100 normal subjects and 45 patients with ALS. In all normal subjects, stimulation of the infraorbital nerve on one side produced bilateral short latency waves, which consisted of a positive/negative wave described with the mean peak latency (P20/N30). The mean square root of the ratio between the amplitude of P20/N30 and the mean rectified surface EMG activity preceding the stimulus was described by A value. RESULTS: The latency of P20 in controls was 18.5 +/- 1.4 ms, N30 was 28.8 +/- 2.8 ms, and the A value was 1.6 +/- 0.5, respectively. In ALS patients, twelve showed absent, seventeen were delayed in the latencies, six were above normal asymmetry on two sides, and ten showed normal. The latency of P20 in ALS patients was 22.9 +/- 9.4 ms, N30 was 33.7 +/- 11.2 ms, and the A value was 1.5 +/- 0.8, respectively. The parameters of the latencies of TCR between ALS patients and the normal controls were statistically different (P < 0.05). CONCLUSIONS: TCR can be reliably measured in all normal subjects and help in disclosing lower brainstem lesions in ALS patients, even without bulbar symptoms.

Adolescent↗
PubMed2004

Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32.

Bcl-2 homology domain (BH) 3-only proteins of the proapoptotic Bcl-2 subfamily play a key role as initiators of mitochondria-dependent apoptosis. To date, at least 10 mammalian BH3-only proteins have been identified, and it is now being realized that they have different roles and mechanisms of regulation in the transduction of apoptotic signals to mitochondria. Hrk/DP5 is one of the mammalian BH3-only proteins implicated in a variety of physiological and pathological apoptosis, yet the molecular mechanism involved in Hrk-mediated apoptosis remains poorly understood. In an attempt to identify cellular proteins participating in Hrk-mediated apoptosis, we have conducted yeast two-hybrid screening for Hrk-interacting proteins and isolated p32, a mitochondrial protein that has been shown to form a channel consisting of its homotrimer. In vitro binding, co-immunoprecipitation, as well as immunocytochemical analyses verified specific interaction and colocalization of Hrk and p32, both of which depended on the presence of the highly conserved C-terminal region of p32. Importantly, Hrk-induced apoptosis was suppressed by the expression of p32 mutants lacking the N-terminal mitochondrial signal sequence (p32(74-282)) and the conserved C-terminal region (p32 (1-221)), which are expected to inhibit binding of Hrk competitively to the endogenous p32 protein and to disrupt the channel function of p32, respectively. Furthermore, small interfering RNA-mediated knockdown of p32 conferred protection against Hrk-induced apoptosis. Altogether, these results suggest that p32 may be a key molecule that links Hrk to mitochondria and is critically involved in the regulation of Hrk-mediated apoptosis.

Amino Acid Sequence↗
PubMed2004

Risk behaviours and benign prostatic hyperplasia.

OBJECTIVE: To identify risk factors for benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: Medical history data, including reported urological conditions and treatments, and risk factor data were collected from 34 694 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial designed to evaluate methods for the early detection of cancer. RESULTS: Asian men had the lowest risks (odds ratio, 95% confidence interval) for nocturia (0.7, 0.5-0.9), physician-diagnosed BPH (0.3, 0.2-0.5) and transurethral prostatectomy (TURP, 0.2, 0.1-0.6), while risks for Whites and Blacks were similar for most measures of BPH. Greater alcohol intake was associated with decreased nocturia (P trend = 0.002), BPH (P trend < 0.001) and TURP (P trend < 0.001). Current tobacco use was associated with decreased nocturia (0.8, 0.7-0.9), BPH (0.7, 0.6-0.8) and TURP (0.6, 0.4-0.8) but dose-response patterns were weak. CONCLUSION: Asian-Americans have the lowest risk of clinical BPH. Alcohol and possibly cigarettes are related to a lower risk for BPH.

Age Distribution↗
PubMed2003

Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women.

A case-control study was performed to assess the potential influence of CYP19 Arg(264)Cys and CYP1B1 Leu(432)Val polymorphisms on breast cancer risk in a series of Korean breast cancer patients and controls. The results suggest that the CYP19 Arg(264)Cys polymorphism modifies breast cancer risk (OR=1.5, 95% CI=1.1-2.2), especially in association with alcohol consumption (P for interaction=0.04), whereas the CYP1B1 Leu(432)Val polymorphism appears to play no role here.

Adult↗
PubMed2002

A protein from the cabbage looper, Trichoplusia ni, regulated by a bacterial infection is homologous to 3-dehydroecdysone 3beta-reductase.

During the screening of immune-regulated genes from the cabbage looper, Trichoplusia ni, a 3-dehydroecdysone 3beta-reductase homologue (DERH) was cloned. In the course of development, 3-dehydroecdysone 3beta-reductase mediates the conversion of 3-dehydroecdysone (3dE) secreted from the prothoracic glands to ecdysone (E), which is subsequently converted to 20-hydroxyecdysone (20E), the major insect molting hormone. The cloned gene is upregulated in fat body during development and is strongly induced after the larva is challenged with bacteria. The gene codes for a 308 amino acid residue protein which shows 42.5% identity to Spodoptera littoralis 3-dehydroecdysone 3beta-reductase. Using the baculovirus expression system, the recombinant DERH was expressed. The purified protein mediates the reduction of 3-dehydromakisterone A to makisterone A, and requires NADPH as a cofactor. Western blots using an antiserum to T. ni DERH revealed the presence of the protein in larval hemolymph and integument. The data indicate that the protein is regulated developmentally and is induced after a challenge with bacteria. Immunohistochemical studies localized the enzyme exclusively in the epidermis and the cuticle.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

8-oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts.

BACKGROUND: Reactive oxygen species (ROS) can cause an oxidative modification of nucleotides, such as 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), which can lead to defects in DNA replication. The misincorporation of 8-oxo-dGTP into DNA is prevented by 8-oxo-dGTPase, which hydrolyzes 8-oxo-dGTP into 8-oxo-dGMP. The changes in this defensive system have not yet been examined in failing hearts, in which the generation of ROS increases. METHODS AND RESULTS: Myocardial infarction (MI) was created in mice by ligating the left coronary artery. Four weeks later, the left ventricle was dilated and contractility was diminished on echocardiography. The generation of ROS, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, increased in the noninfarcted left ventricle from MI mice. The formation of thiobarbituric acid-reactive substances also increased in the mitochondria from MI mice. 8-Oxo-dGTPase was detected in the mitochondrial fractions isolated from MI mice using a Western blot analysis with an antibody to its human homologue (hMTH1). Immunohistochemistry showed positive staining for hMTH1 was localized in the cardiac myocytes. CONCLUSIONS: The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage. As a result, 8-oxo-dGTPase is considered a useful marker of mitochondrial oxidative stress in heart failure.

Animals↗