PubMed Health⌕ Search

Biomedical subjects

D Kang

Publications and source records attributed to D Kang.

At least 55 records · Page 3Linked to original sources
PubMed2000

Molecular characterization of prostate carcinoma tumor antigen-1, PCTA-1, a human galectin-8 related gene.

The galectin family of proteins has been associated with several diverse cellular processes. More than 30 years since the discovery of the first member, precise biological functions for the family as a whole, or for individual members has proven elusive. The isolation of Prostate Carcinoma Tumor Antigen-1 (PCTA-1), a cDNA closely related to rat and human Galectin-8, as a surface marker associated with prostate cancer was achieved using a previously described immunological subtraction approach, Surface Epitope Masking (SEM) approach, in combination with expression screening. It appears that PCTA-1 expression is almost ubiquitous in normal human tissues and could alter in specific contexts such as transformation or metastasis. Multiple expression isoforms of PCTA-1 at the mRNA level are observed. PCTA-1 maps to 1q42-43, a locus associated with predisposition to prostate cancer. We have determined the genomic structure of PCTA-1 to account for the several observed isoforms, performed expression analysis to determine distribution in normal and transformed contexts at the RNA and protein level and conducted over-expression studies to determine effects on cellular phenotype.

3' Untranslated Regions↗
PubMed2000

Binding of human mitochondrial transcription factor A, an HMG box protein, to a four-way DNA junction.

Mitochondrial transcription factor A (mtTFA), the only known transcription factor in mitochondria, is also implicated in maintenance of mitochondrial genome although little is elucidated about its molecular basis. mtTFA is a member of HMG box proteins family. Some HMG proteins bind with high affinity to four-way DNA junctions that mimic a Holliday structure, a putative intermediate in DNA recombination. To explore possible involvement of a Holliday-like structure in the maintenance of mitochondrial genome, we examine the binding of recombinant human mtTFA to a synthetic four-way DNA junction. The human mtTFA binds to the four-way DNA junction with an approximately 10-fold higher affinity than to the corresponding linear duplex DNA and with essentially the same affinity as to a 40-mer DNA containing the human mitochondrial light strand promoter sequence. The mtTFA binds to the four-way as a monomer. Both of the two HMG box domains of human mtTFA are required for the high affinity binding to the four-way junction.

Base Sequence↗
PubMed2000

Accumulation of adenine DNA glycosylase-sensitive sites in human mitochondrial DNA.

The mitochondrial respiratory chain inevitably produces reactive oxygen species as byproducts of aerobic ATP synthesis. Mitochondrial DNA (mtDNA), which is located close to the respiratory chain, is reported to contain much more 8-oxoguanine (8-oxoG), an oxidatively modified guanine base, than nuclear DNA. Despite such a high amount of 8-oxoG in mtDNA (1-2 8-oxoG/10(4) G), mtDNA is barely cleaved by an 8-oxoG DNA glycosylase or MutM, which specifically excises 8-oxoG from a C:8-oxoG pair. We find here that about half of human mtDNA molecules are cleaved by another 8-oxoG-recognizing enzyme, an adenine DNA glycosylase or MutY, which excises adenine from an A:8-oxoG pair. The cleavage sites are mapped to adenines. The calculated number of MutY-sensitive sites in mtDNA is approximately 1.4/10(4) G. This value roughly corresponds with the electrochemically measured amount of 8-oxoG in mtDNA (2.2/10(4) G), raising the possibility that 8-oxoG mainly accumulates as an A:8-oxoG pair.

Adenine↗
PubMed2000

Trichoplusia ni lebocin, an inducible immune gene with a downstream insertion element.

A cDNA clone encoding a lebocin-like protein was obtained from the cabbage looper Trichoplusia ni by using differential display PCR. Northern blot analysis showed that lebocin gene expression was inducible upon bacterial challenge. Transcripts were mainly found in fat body but were also observed in hemocytes. Expression reached its highest level at 20 h and continued at least until 60 h after bacterial injection. The deduced protein is proline-rich and contains 143 amino acid residues. At position 128, a possible O-glycosylation site is observed. The whole protein shows 35% identity to Bombyx mori lebocin. The mature peptide displays an N-terminus similar to that of lebocin and a C-terminus to that of Drosophila metchnikowin. A 39-bp repetitive element is located downstream of the coding region.

Amino Acid Sequence↗
PubMed2000

Molecular phenotype of the human oocyte by PCR-SAGE.

Consecutive application of PCR and serial analysis of gene expression (SAGE) was used to generate a catalog of approximately 50, 000 SAGEtags from nine human oocytes. Matches for known genes were identified using the National Institutes of Health SAGEtag database. This database links directly to the UniGene database, providing rapid discrimination between SAGEtags that match known genes and expressed sequence tags and those that currently have no match. Matches in the oocyte SAGE catalog were found for surface receptors, second-messenger systems, and cytoskeletal, apoptotic, and secreted proteins. Many of these proteins were not previously known to be expressed in mammalian oocytes. The relative abundances of transcripts for cytoskeletal proteins and proteins known to be in oocytes are consistent with their documented expression, suggesting an absence of representational distortion by the PCR step. The expression profile of the human oocyte may help identify factors that reprogram somatic cell nuclei to totipotency.

Databases, Factual↗
PubMed2000

Localization of P32 protein (gC1q-R) in mitochondria and at specific extramitochondrial locations in normal tissues.

P32 protein, also known as the gC1q receptor for complement component C1q, is a binding protein for nuclear pre-mRNA splicing factor SF2/ASF and numerous other nuclear and cell surface proteins, yet is targeted to the mitochondrial matrix compartment where these proteins are not present. In the present study, we use immunogold electron microscopy to evaluate the subcellular distribution of P32 protein (gC1q-R) in cultured cell lines and in rat tissues embedded in the acrylic resin LR Gold. Immunogold labeling of Raji lymphoma, CHO, human fibroblasts, HeLa and B-SC-1 cells shows reactivity primarily within mitochondria. Highly specific labeling of mitochondria is also obtained in rat tissues, including adrenal gland, cerebellum, cerebral cortex, heart, kidney, liver, pituitary, pancreas, skeletal muscle, spleen, testes and thyroid. However, strong P32 (gClq-R) reactivity is also present in (i) zymogen granules, condensing vacuoles, endoplasmic reticulum, and on the cell surface of pancreatic acinar cells, (ii) on the cell surface of microvascular endothelial cells in pancreas and kidney, (iii) on the cell surface and in nuclei of splenic lymphocytes, and (iv) in the acrosome of developing spermatids in testes. Western immunoblots show that the polyclonal antibody to P32 (gC1q-R) used in this study reacts specifically with a 32-kDa protein in both purified pancreatic zymogen granules and in mitochondria, and no other proteins are reactive. These results provide evidence that P32 (gC1q-R) is a mitochondrial protein that also localizes outside mitochondria in certain cells and tissues under normal physiological conditions.

Animals↗
PubMed2000

Association of the vitamin D receptor start codon polymorphism (FokI) with bone mineral density in postmenopausal Korean women.

We undertook this study in order to examine the association between bone mineral density (BMD) and a polymorphism at the first of two potential translation initiation codons in the vitamin D receptor (VDR) gene. This polymorphism was detected by restriction fragment length polymorphism analysis, using polymerase chain reaction (PCR) and the restriction endonuclease FokI. The f allele indicates the presence of the FokI site, and the F allele its absence. The FokI genotype was determined in 174 postmenopausal Korean women, aged 43-71 years. The distribution of FokI genotypes in Koreans was found not to differ significantly from those found in Caucasians and Japanese, although it does differ significantly from that found in the black American population. We observed a significant association between the FokI polymorphism and lumbar BMD; P = 0.048, analysis of covariance [ANCOVA], but no association with femoral neck BMD (P = 0.505, ANCOVA). Those with the ff genotype had a 13.3% lower BMD in the lumbar spine than the FF subjects. In addition, a significantly higher prevalence of the ff genotype was observed in osteoporotic compared with osteopenic or normal women (P = 0.036, chi2 test). These data suggest that the ff genotype of the VDR gene correlates with decreased BMD in the lumbar spine in postmenopausal Korean women.

Base Sequence↗
PubMed2000

Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1.

The expansion of an unstable CAG repeat causes spinocerebellar ataxia type 1 (SCA1) and several other neurodegenerative diseases. How polyglutamine expansions render the resulting proteins toxic to neurons, however, remains elusive. Hypothesizing that long polyglutamine tracts alter gene expression, we found certain neuronal genes involved in signal transduction and calcium homeostasis sequentially downregulated in SCA1 mice. These genes were abundant in Purkinje cells, the primary site of SCA1 pathogenesis; moreover, their downregulation was mediated by expanded ataxin-1 and occurred before detectable pathology. Similar downregulation occurred in SCA1 human tissues. Altered gene expression may be the earliest mediator of polyglutamine toxicity.

Amino Acid Transport System X-AG↗
PubMed2000

A gain-of-function phenotype conferred by over-expression of functional subunits of the COP9 signalosome in Arabidopsis.

The COP9 signalosome is a conserved cellular regulator present in diverse organisms. To understand the structural and functional relationship of the COP9 signalosome with its subunits, we expressed in wild-type and mutant Arabidopsis backgrounds two orthologues of subunit 1, rice FUS6 (rFUS6) and human GPS1, and Arabidopsis subunit 8 (COP9). In Arabidopsis, rFUS6 can functionally replace Arabidopsis endogenous FUS6 to form the COP9 signalosome complex and rescue the null fus6-1 mutant phenotype. Moreover, light-grown rFUS6 over-expression seedlings displayed longer hypocotyls and reduced anthocyanin accumulation in comparison to wild-type seedlings, which is opposite to the fus6/cop11 mutant phenotype. The long-hypocotyl phenotype was also observed in transgenic seedlings over-expressing Arabidopsis COP9. This finding indicates that over-expression of a functional subunit 1 or subunit 8 of the COP9 signalosome confers a gain-of-function phenotype relative to the complex. Human GPS1, when expressed in the fus6-1 null mutant of Arabidopsis, can assemble into a chimeric COP9 signalosome at low efficiency, demonstrating the structural conservation of the complexes between human and Arabidopsis. This low-abundancy chimeric complex is insufficient to fully rescue the mutant but is able to attenuate the mutant severity.

Amino Acid Sequence↗
PubMed2000

The D-loop structure of human mtDNA is destabilized directly by 1-methyl-4-phenylpyridinium ion (MPP+), a parkinsonism-causing toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine has been reported to cause parkinsonism via its neurotoxic form, 1-methyl-4-phenylpyridinium ion (MPP+), which inhibits complex I of the mitochondrial respiratory chain. Its parkinsonism-causing mechanisms attract a great deal of interest as a model of the disease. Recently, we reported that MPP+ strongly decreases the amount of mtDNA independent of the inhibition of complex I. Maintenance of a proper amount of mtDNA is essential for the normal function of mitochondria as exemplified in many mitochondrial diseases. The most characteristic feature in vertebral mtDNA replication is that H-strand synthesis proceeds displacing the parental H-strand as a long single strand. It forms the D-loop, a triplex replication intermediate composed of the parental L-strand, nascent H-strand and displaced H-strand. Here we show that MPP+ does not inhibit DNA synthesis by DNA polymerase gamma, but rather releases the nascent H-strands from mtDNA both in organello and in vitro. This indicates that MPP+ directly destabilizes the D-loop structure, thereby inhibiting replication. This study raises a new mechanism, i.e. destabilization of replication intermediates, for depletion of mtDNA.

1-Methyl-4-phenylpyridinium↗
PubMed2000

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk.

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6

Adult↗
PubMed2000

Association of serum lipids and glucose with the risk of colorectal adenomatous polyp in men: a case-control study in Korea.

Previous studies on life style for colorectal cancer risk suggest that serum lipids and glucose might be related to adenomatous polyps as well as to colorectal carcinogenesis. This case-control study was conducted to investigate the associations between serum lipids, blood glucose, and other factors and the risk of colorectal adenomatous polyp. Male cases with colorectal adenomatous polyp, histologically confirmed by colonoscopy (n=134), and the same number of male controls matched by age for men were selected in hospitals in Seoul, Korea between January 1997 and October 1998. Serum lipids and glucose levels were tested after the subjects had fasted for at least 12 hr. Conditional logistic regression showed that there was a significant trend of increasing adenomatous polyp risk with the rise in serum cholesterol level (Ptrend=0.07). Increasing trend for the risk with triglyceride was also seen (Ptrend=0.01). HDL-cholesterol and LDL-cholesterol had increasing trends for the risk, which were not significant. In particular, it was noted that higher fasting blood glucose level reduced the adenomatous polyp risk for men (Ptrend=0.001). This study concluded that both serum cholesterol and triglyceride were positively related to the increased risk for colorectal adenomatous polyp in Korea. Findings on an inverse relationship between serum glucose and the risk should be pursued in further studies.

Adenomatous Polyps↗
PubMed2000

FK506 attenuates developing and established joint inflammation and suppresses interleukin 6 and nitric oxide expression in bacterial cell wall induced polyarthritis.

OBJECTIVE: To determine the efficacy of therapeutic administration of FK506 (Tacrolimus) in suppressing developing and established joint inflammation, proinflammatory cytokine expression, and nitric oxide (NO) production in peptidoglycan-polysaccharide (PG/PS) induced experimental polyarthritis in rats. METHODS: Chronic joint inflammation was induced by intraperitoneal injection of PG/PS, and joint inflammation was quantified using arthritis index and paw volume. Serum and joint levels of interleukin 6 (IL-6) were measured by bioassay and Western blot analysis respectively, and serum levels of NO production were determined by the Griess procedure and the expression of the inducible isoform of nitric oxide synthase (i-NOS) in the joints was determined by Western blot analysis. RESULTS: Arthritis induced by PG/PS is biphasic, progressing through an initial acute phase and a remission phase, which is followed by a persistent chronic phase. Daily administration of FK506 initiated during the remission phase significantly attenuated the onset and development of chronic joint inflammation. We observed a significant reduction in joint inflammation and swelling, an apparent suppression of pannus development, and minimal erosive damage to the articular cartilage and subchondral bone. Fully established chronic joint inflammation was also ameliorated by daily administration of FK506. Joint swelling and inflammation was significantly reduced by 5 days post-treatment with FK506 and the erosive activity associated with the pannus appeared diminished. The elevated expression of IL-6 and NO characteristic of chronic joint inflammation in the serum and in joint tissue was significantly reduced by FK506 treatment. CONCLUSION: Therapeutic administration of FK506 has a profound antiinflammatory effect on the development of the chronic, erosive arthritis induced by PG/PS. This attenuation in joint inflammation was associated with suppression of IL-6 and NO production systemically and locally in the joints. Our data suggest that FK506 may be effective in the treatment of chronic joint inflammation associated with rheumatoid arthritis.

Animals↗
PubMed2000

[Analysis on the characteristic and trend of AIDS epidemics in Shandong].

OBJECTIVE: To analyse the data thru labs and field epidemiological investigation from 1987 to 1999, in order to find out the characteristics, sources of infections and its trend which would lead to the development of strategy, prevention and control of AIDS in Shandong. METHODS: Anti-HIV antibody was detected by ELISA and WB in the serum of high-risk groups. When Anti-HIV antibody was positive, personal and epidemiological history was investigated. The anticoagulated blood was repeatedly collected to verify the infected people. PBMCs were separated from the anticoagulated blood to collect previrus DNA. Gene sequence was then detected and subtype analysed by PCR using ABI company kit. RESULTS: Eight hundred five thousand eight hundred and one specimens were detected in the whole province from 1987 to 1999. 52 cases showed Anti-HIV antibody positive, with a rate of 0.06 per thousand. Of the 52 cases, 2 died. Sequence detection and subtype analysis of PBMC in 24 infected people showed that there were five HIV-1 subtypes M: A, B, B', C, E which were from 7 cities of the province. Blood and sexual transmission took the majority with proportions, 59.62% and 30.76% respectively. The subtypes from 13 blood donors were all B'. Among 10 labourers refurned from abroad and 1 spouse six cases were C, two were B, and another two were A and E subtypes respectively. Epidemiologic data showed that most of the infected people were mobile, making sexual transmission easy to occur. CONCLUSION: The moods of HIV/AIDS transmission in Shandong were mainly through blood and sexual contacts.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[A simple biostatistical method for meta analysis of the data on 2 x 2 table].

Meta-analysis is a method in common use for data analysis in evidence-based medicine. In this paper, based on the Mantel-Haenszel and Peto methods used for Meta-analysis of the data on 2 x 2 table, we put forward a simple calculating method for clinicians. It is useful for Meta-analysis and can be easily applied to analysis of the data from multi-studies in evidence-based medicine.

Biometry↗
PubMed1999

Urinary 1-hydroxypyrene and other PAH metabolites as biomarkers of exposure to environmental PAH in air particulate matter.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from occupational, environmental, medicinal and dietary sources. PAH metabolites in human urine can be used as biomarkers of internal dose to assess recent exposure to PAHs. The most widely used urinary PAH metabolites are 1-hydroxypyrene (1-OHP) or 1-hydroxypyrene-O-glucuronide (1-OHP-gluc), the major form of 1-OHP in human urine, because of their relatively high concentration and prevalence in urine and their relative ease of measurement. Elevated levels of 1-OHP or 1-OHP-gluc have been demonstrated in smokers, in patients receiving coal tar treatment (vs. pre-treatment), in postshift road pavers or coke oven workers, and in subjects ingesting charbroiled meat. This metabolite is found (at low levels) in most human urine samples, even in persons without apparent occupational or smoking exposure. Recent studies suggest that environmental exposure to PAHs (and air particles) is associated with increased excretion of 1-OHP-gluc or 1-OHP. These findings raise the possibility of using urinary concentration of 1-OHP-gluc, or another PAH metabolite, as a surrogate biomarker of exposure to airborne fine (sooty) particulate matter--the major source of PAHs in polluted air. Reported associations between ambient particulate matter concentrations and health effects among adults and children, including respiratory disease and mortality, indicate the need for biomarkers of fine particle exposure. If validated, such biomarkers would be useful in supplementing and refining exposure information obtained by ambient monitoring.

Adult↗
PubMed1999

Comparison of three analytical methods for 1-hydroxypyrene glucuronide in urine after non-occupational exposure to polycyclic aromatic hydrocarbons.

Urinary pyrene metabolites, 1-OHP and 1-OHPG, have been used as biomarkers for the assessment of occupational and environmental exposure to PAHs. This study compares the sensitivity and applicability of the different analytical methods of 1-OHPG for human biomonitoring of low level exposure to PAHs. Three analytical methods were compared: (1) HPLC method from that reported by Singh et al. (Singh, R., Tucek, M., Maxa, K., Tenglerova, J., Weyand, E.H., 1995. A rapid and simple method for the analysis of 1-hydroxypyrene glucuronide: a potential biomarker for polycyclic aromatic hydrocarbon exposure. Carcinogenesis 16, 2909-2915); (2) IAC-SFS method: the rapid and simple assay using IAC purification using monoclonal antibody specific for PAH-DNA adduct and PAH metabolites and SFS quantitation; and (3) IAC-HPLC method: IAC and HPLC separation and quantitation. The correlation between the IAC-SFS method, HPLC method, and the IAC-SFS method was determined in 20 first year-grade junior high school students (age 12-13) from Yochon, Korea who participated in a nationwide survey for the environmental disease surveillance projects in Korea. Chromatograms obtained by the IAC purification and HPLC quantitation method were clear with no interfering peaks adjacent to 1-OHPG, thus 1-OHPG could be easily quantitated. However, the HPLC method produced chromatogram profiles with many interfering peaks adjacent to 1-OHPG peak. The concentrations of 1-OHPG in 20 urine samples were similar when analyzed by all three analytical methods. The correlation coefficient between the IAC-HPLC and IAC-SFS methods was 0.915, and between the IAC-HPLC and HPLC methods was 0.844, and between the IAC-SFS and HPLC methods was 0.805. The analytical methods for 1-OHPG compared in this study showed a good correlation with one another. These results suggest that any of the methods can be applied to human biomonitoring of PAH exposure. However, SFS quantitation after IAC purification is rapid and simple because this method does not need HPLC separation of 1-OHPG.

Adolescent↗