Biomedical subjects

Young Joo Kim

Publications and source records attributed to Young Joo Kim.

At least 19 recordsLinked to original sources

PubMed2006

Development of acetylated HDD kit for preparation of 188Re-HDD/lipiodol.

A lipiodol solution of (188)Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol ((188)Re-HDD/lipiodol) is in clinical study for liver cancer therapy. However, formulation of it is difficult due to highly active and unstable sulfhydryl groups. We produced new kits using diacetylated HDD (AHDD), in which sulfhydryl groups are protected. We found that AHDD kit can replace HDD kit due to an increased stability for formulation, the better radiolabeling efficiency (78%) and the equivalent biodistribution pattern in mice.

Acetylation↗

PubMed2006

SNP@Domain: a web resource of single nucleotide polymorphisms (SNPs) within protein domain structures and sequences.

The single nucleotide polymorphisms (SNPs) in conserved protein regions have been thought to be strong candidates that alter protein functions. Thus, we have developed SNP@Domain, a web resource, to identify SNPs within human protein domains. We annotated SNPs from dbSNP with protein structure-based as well as sequence-based domains: (i) structure-based using SCOP and (ii) sequence-based using Pfam to avoid conflicts from two domain assignment methodologies. Users can investigate SNPs within protein domains with 2D and 3D maps. We expect this visual annotation of SNPs within protein domains will help scientists select and interpret SNPs associated with diseases. A web interface for the SNP@Domain is freely available at http://snpnavigator.net/ and from http://bioportal.net/.

Computer Graphics↗

PubMed2006

An improved method of 18F peptide labeling: hydrazone formation with HYNIC-conjugated c(RGDyK).

Radiolabeled alpha(v)beta(3)-integrin antagonists are increasingly investigated as a means of imaging angiogenesis. Several methods of labeling alpha(v)beta(3)-integrin binding peptide with (18)F have been reported recently. In the present study, we devised a straightforward means for labeling Arg-Gly-Asp (RGD) peptide with (18)F via hydrazone formation between c(RGDyK)-hydrazinonicotinic acid (HYNIC) (3) and 4-[(18)F]-fluorobenzaldehyde ([(18)F]4). The resulting reaction mixture was purified by HPLC to give 4'-[(18)F]-fluorobenzylidenehydrazone-6-nicotinamide-c(RGDyK) ([(18)F]5). The conjugation efficiency of 3 and 4 to form [(18)F]5 was 95.2%, and the radiochemical purity of [(18)F]5 after purification was >99%. The specific activity of [(18)F]5 estimated by radio-HPLC was 20.5 GBq/mumol (end of synthesis). Competitive binding assay of c(RGDyK) (1) and 5 was performed using [(125)I]iodo-c(RGDyK) as a radioligand, and K(i) values were found to be 2.8 and 21.7 nM, respectively. For the biodistribution study, the angiogenic mouse model was established by inducing unilateral ischemia on the left hindlimbs of ICR mice after femoral artery ablation. Seven days after inducing ischemia, [(18)F]5 was administered to the mice through the tail vein. Ischemic muscle uptake of [(18)F]5 was significantly higher than that of normal muscle (P<.01). Specific uptake was confirmed by coinjection of 1 with [(18)F]5. Here, we successfully labeled RGD peptide with (18)F via hydrazone formation between 3 and 4, resulting to [(18)F]5. [(18)F]5 was found to have high affinity for alpha(v)beta(3)-integrin and to accumulate specifically in ischemic hindlimb muscle of mice. We suggest that (18)F labeling via formation of hydrazone between HYNIC peptide and [(18)F]4 is a useful method for labeling c(RGDyK), which can be applied for imaging angiogenesis.

Animals↗

PubMed2006

Chemical modification of siRNAs to improve serum stability without loss of efficacy.

Development of RNA interference as a novel class of therapeutics requires improved pharmacokinetic properties of short interfering RNA (siRNA). To confer enhanced serum stability to Sur10058, a hyperfunctional siRNA which targets survivin mRNA, a systematic modification at the 2'-sugar position and phosphodiester linkage was introduced into Sur10058. End modification of three terminal nucleotides by 2'-OMe and phosphorothioate substitutions resulted in a modest increase in serum stability, with 3' end modification being more effective. Alternating modification by 2'-OMe substitution significantly stabilized Sur10058, whereas phosphorothioate modification was only marginally effective. Through various combinations of 2'-OMe, 2'-F and phosphorothioate modifications that were directed mainly at pyrimidine nucleotides, we have identified several remarkably stable as well as efficient forms of Sur10058. Thus, our results provide an effective means to stabilize siRNA in human serum without compromising the knockdown efficiency. This advancement will prove useful for augmenting the in vivo potency of RNA interference.

Base Sequence↗

PubMed2006

Comparative study of the linkage disequilibrium of an ENCODE region, chromosome 7p15, in Korean, Japanese, and Han Chinese samples.

The extent and pattern of linkage disequilibrium (LD) in the human genome provide important information for disease gene mapping. Previous studies have shown that LDs vary depending on chromosomal regions and populations. As the Asian samples of the International HapMap Project consisted of Japanese and Chinese populations, it was of interest whether we could use the HapMap data as a reference to carry out association studies of common complex diseases in a closely related population, such as Koreans. We have compared the LD and recombination patterns defined by single-nucleotide polymorphisms (SNPs) in ENCODE region ENm010, chromosome 7p15.2, in Korean, Japanese, and Chinese samples and further tested the robustness of tagSNPs among the Asian samples. We genotyped 792 SNPs in 500 kb (chromosome 7: 26699793-27199792, NCBI build 34) from 90 unrelated Koreans by fluorescence polarization detection and compared the data with Asian data from the HapMap project. Despite some differences in the position of high LD region boundaries, the overall patterns of LD were remarkably similar across the three samples, reflecting strong genetic affinities among them. Furthermore, the haplotype tag SNP transferability across the three samples was greater than 90%. Our results support the initial suggestion that the populations genotyped in the HapMap project might serve as reference populations for the selection of tagSNPs in association studies.

Alleles↗

PubMed2006

Central obesity as a risk factor for prostatic hyperplasia.

OBJECTIVE: Obesity-related metabolic diseases may influence prostatic hyperplasia. This study examined the impact of obesity on prostate volume in men without overt obesity-related metabolic diseases. RESEARCH METHODS AND PROCEDURES: We recruited 146 men over the age of 40 years who did not have overt obesity-related diseases, such as diabetes, impaired fasting glucose, hypertension, or dyslipidemia. Transrectal ultrasonography was performed on all subjects. The subjects were divided into three groups according to their BMI: normal (18.5 to 22.9 kg/m2), overweight (23 to 24.9 kg/m2), and obese (> or = 25 kg/m2), and two groups according to their waist circumference: normal waist (< or = 90 cm) and central obesity (> 90 cm). The classification of the subgroups was based on the Asia-Pacific criteria of obesity. We compared the prostate volume among subgroups and assessed factors related to prostatic hyperplasia. RESULTS: Mean prostate volume was 18.8 +/- 5.0, 21.8 +/- 7.2, and 21.8 +/- 5.6 mL in the normal, overweight, and obese groups, respectively, and was 20.0 +/- 5.9 and 23.7 +/- 5.3 mL in the normal waist and central obesity group, respectively. Prostate volume was significantly greater in the obese group than in the normal group (P = 0.03) and in the central obesity group compared with the normal waist group (P = 0.002). Prostate volume was positively correlated with BMI and waist circumference after adjustment for age. After adjusting for confounding factors, central obesity was an independent factor affecting prostatic hyperplasia, which was defined as a prostate volume > 20 mL (odds ratio = 3.37, p = 0.037). Relative to men with both low BMI (18.5 to 22.9 kg/m2) and normal waist circumference, those with high BMI (> or = 25 kg/m2) and central obesity were at significantly increased risk of prostatic hyperplasia (odds ratio = 4.88, p = 0.008). However, those with high BMI (> or = 25 kg/m2) and normal waist circumference were not at significantly increased risk. DISCUSSION: Prostate volume was greater in the obese and central obesity groups than in the normal group after patients with overt obesity-related metabolic diseases were excluded. Although both BMI and waist circumference were positively correlated with prostate volume, central obesity was the only independent factor affecting prostate hyperplasia. We suggest that central obesity is an important risk factor for prostatic hyperplasia.

Abdominal Fat↗

PubMed2005

FESD: a Functional Element SNPs Database in human.

We have created the Functional Element SNPs Database (FESD) that categorizes functional elements in human genic regions and provides a set of single nucleotide polymorphisms (SNPs) located within each area. In the FESD, the human genic regions were divided into 10 different functional elements, such as promoter regions, CpG islands, 5'-untranslated regions (5'-UTRs), translation start sites, splice sites, coding exons, introns, translation stop sites, polyadenylation signals and 3'-UTRs, and subsequently, all the known SNPs were assigned to each functional element at their respective position. With the FESD web interface, users can select a set of SNPs in the specific functional elements and get their flanking sequences for genotyping experiments, which will help in finding mutations that contribute to the common and polygenic diseases. A web interface for the FESD is freely available at http://combio.kribb.re.kr/ksnp/resd/.

Databases, Nucleic Acid↗

PubMed2005

Multifunctional drug delivery system using starch-alginate beads for controlled release.

Utilizing starch-containing alginate beads, a novel drug delivery system (DDS) was developed. With the starch inside, the composite bead could be dried in its original bead shape and handled in the dried state. By employing alginate multi-coating strategy on the starch-alginate beads, detained or controlled release was efficiently achieved and successfully demonstrated for a model peptide drug, L-phenylalanine. The initial latent time and release rate of the drug inside the beads were able to be controlled simply by varying the number of multi-coatings. While the latent time for the initial release was negligible for non-coated starch-alginate beads, the latent times of beads coated one, two, and four times increased to 15, 30, and 70 min, respectively. Furthermore, the alginate component of the composite beads could adsorb and remove heavy metals such as lead from the body. These multifunctional beads combined with the novel coating process will greatly benefit alginate gel-based DDS.

Alginates↗

PubMed2004

The finding of new genetic polymorphism of UCP-1 A-1766G and its effects on body fat accumulation.

A-1766G polymorphism, for the first time, has been found in the sequencing of pooled and individual genomic DNA of Korean subjects at the 5' flanking region of the UCP-1 gene. The effects of new polymorphism on body fat were elucidated among 387 Korean female subjects. It was shown that the genotypes AA, AG, and GG were consisted of 57.4%, 37.7%, and 4.9%, respectively, which was in agreement with Hardy-Weinberg equilibrium (P=0.327). The frequency of major A allele was 0.762 and that of minor G allele was 0.238. It is found that the waist-hip ratio (WHR) (P=0.008), body fat mass (P=0.023), and percent body fat (P=0.014) are significantly higher in the AG/GG type compared to the AA type. When the subjects were analyzed using computerized tomography, there were significant increases in the AG/GG type compared to the AA type in the abdominal subcutaneous fat (P=0.015) and the abdominal visceral fat (P=0.013), respectively. A-1766G is approximately 2 kb downstream from the well-known A-3826G polymorphism, and no linkage between them was found (D'=0.929, R(2)=0.283). Three haplotypes (frequency >0.05) were examined from two polymorphisms and studied for their physiological effects. It was found that haplotype [GG] was significantly associated with increased body fat, while haplotype [GA] was associated with decreased body fat.

Adipose Tissue↗

PubMed2004

Bioinformatics in the post-genome era.

Recent years saw a dramatic increase in genomic and proteomic data in public archives. Now with the complete genome sequences of human and other species in hand, detailed analyses of the genome sequences will undoubtedly improve our understanding of biological systems and at the same time require sophisticated bioinformatic tools. Here we review what computational challenges are ahead and what are the new exciting developments in this exciting field.

Animals↗

PubMed2004

Expression of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 and -2 in intraductal and nonintraductal growth type of cholangiocarcinoma.

BACKGROUND: The intraductal growth (IG) type of cholangiocarcinoma has a better prognosis than the mass forming (MF) and periductal infiltrating (PI) types. Matrix metalloproteinase (MMP)-2 and MMP-9, regulated by tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-1, respectively, play important roles in the degradation of the basement membrane during tumor invasion. Alteration in MMPs and TIMPs may regulate the gross morphology of cholangiocarcinoma. METHODS: MMP-2 and MMP-9 were analyzed in 35 cholangiocarcinomas and 4 normal livers with fresh tissue using zymography and real-time reverse transcription-polymerase chain reaction (RT-PCR), and expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 were evaluated in 76 cholangiocarcinomas by immunohistochemistry. RESULTS: Activity of MMP-2 and its active form were detected in 80% and 57% of cholangiocarcinomas respectively. The total MMP-2, active 62 kDa MMP-2, and MMP-2 mRNA increased 5.4 and 8.2 times, 4.4 and 10.9 times, and 2.9 and 5.8 times in the MF and PI types, respectively, compared to the IG type. The majority of MMP-9 was in the proform and active 82 kDa MMP-9 was detected in 9% of cholangiocarcinomas. MMP-9 revealed no significant difference in relation to the gross types. The balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 were significantly decreased in the MF and PI types, compared to the IG type. In the normal and nonneoplastic livers, the expressions of MMP-2 and MMP-9 were very low without active forms. CONCLUSIONS: The activities of MMP-2 and loss of balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 are suggested as playing important roles in invasive growth related to the gross type of cholangiocarcinoma.

Adult↗

PubMed2004

Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging.

BACKGROUND AND AIM: Various mannose receptor-binding agents, for example 99mTc-diethylenetriaminepentaacetic acid (DTPA)-mannosyl-polymer, have been developed for sentinel lymph node (SLN) imaging. In order to simplify the synthesis and labelling procedure and to improve the biological properties, we developed a novel mannose receptor-binding agent, 99mTc-neomannosyl human serum albumin (99mTc-MSA), for SLN imaging. METHODS: MSA was synthesized by conjugating mannopyranosylphenylisothiocyanate to human serum albumin (HSA). After reducing MSA with beta-mercaptoethanol and PD-10 column purification, a medronate solution containing stannous fluoride was added, divided into aliquots and freeze-dried. Reduced MSA was labelled with 99mTc-pertechnetate solution. The stability was checked for 24 h at 37 degrees C in human serum. The biodistribution of 99mTc-MSA in mice was investigated by intravenous injection through the tail vein and subcutaneous injection into the foot pad. The biodistributions of 99mTc-HSA and 99mTc-antimony sulphur colloid (99mTc-ASC) were also investigated for comparison. Dynamic whole-body images were obtained for 30 min after subcutaneous injection into the rats' foot pads. RESULTS: The number of mannose molecules conjugated per MSA was 15.9. The number of thiol groups produced was 19.4 per MSA after reduction with beta-mercaptoethanol. Labelling yields were always higher than 97%. 99mTc-MSA was stable for 24 h at 37 degrees C in human serum. The biodistribution in mice after intravenous injection showed high liver uptake (50.7+/-5.5% and 42.7+/-3.7% injected dose per gram at 10 and 60 min, respectively). 99mTc-MSA and 99mTc-ASC showed high accumulation in the lymph nodes after subcutaneous injection, whereas 99mTc-HSA and Tc-tin colloid did not, in both biodistribution and imaging studies. CONCLUSIONS: We have successfully developed a novel 99mTc-MSA for lymphoscintigraphy. The results of animal studies show that 99mTc-MSA has promising properties for SLN imaging.

Animals↗

PubMed2004

Contribution of specific foods to fat, fatty acids, and cholesterol in the development of a food frequency questionnaire in Koreans.

The present study identified dietary sources of fat, fatty acids, and cholesterol in Koreans residing in and near Seoul. The study also identified foods to be included in a food frequency questionnaire (FFQ) by both contribution analysis (CA) and multiple regression analysis (MRA). Three-day dietary records were collected from 224 subjects (107 men and 117 women) aged 30 to 85 years. Pork was the main source of total fat and the largest contributor to saturated fatty acids (SFA) was beef. MRA identified animal food as the primary source of between-person variance for SFA. Arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid originated primarily from marine products. About a fourth of the total cholesterol intake was derived from chickens' eggs by CA, while chickens' eggs accounted for 46% of the cholesterol intake for between-person variance by MRA. With 10 food items, the FFQ could explain more than half of total intakes except for total fat and n-3 polyunsaturated fatty acids (PUFA), and at least 65% of between-person variances. The percentage coverage in the FFQ ranged from 61% for n-6 PUFA and linoleic acid and to 90% for arachidonic acid. The value of this FFQ is that it can estimate usual dietary food patterns and nutrient intake in Koreans for epidemiological studies. It can also potentially be used to study the relationship between specific diseases and nutrient intakes of interest.

Adult↗

PubMed2003

Association of tumor necrosis factor polymorphisms with asthma and serum total IgE.

Tumor necrosis factors (TNF; TNFA and TNFB) are major pro-inflammatory cytokines that are thought to be important in the pathogenesis of asthma. However, the functions of genetic polymorphisms in these cytokines have not been thoroughly examined in the context of asthma pathology. In an effort to discover polymorphism(s) in genes whose variant(s) have been implicated in asthma phenotypes, we examined the genetic effects of TNF (TNFA and TNFB) polymorphisms on asthma and total serum IgE level. Seven common single-nucleotide polymorphisms (SNP) in TNF genes were genotyped in a Korean asthma cohort (asthmatics n=550, normal controls n=171). Six common haplotypes could be constructed in the TNF gene cluster due to very strong LD between TNFA and TNFB, located 13 kb apart on chromosome 6p21. One SNP (TNFA-308G>A) showed a significant association with the risk of asthma (P=0.0004). The frequency of TNFA-308A allele-containing genotype in asthmatics (9.8%) was much lower than that in normal controls (22.9%). The protective effects of this polymorphism on asthma were also evident in separated subgroups by atopic status (P=0.05 in non-atopic subjects and P=0.003 in atopic subjects). The most common haplotype of the TNF gene (TNF-ht1[GGTCCGG]) was associated with total serum IgE (immunoglobulin E) levels in asthma patients, especially in non-atopic patients (P=0.004). Genetic variants of TNF might be involved in development of asthma and total serum IgE level in bronchial asthma patients. The results of this study could be helpful to understand the function of important TNF genes in asthma and IgE production.

Adolescent↗

PubMed2003

Repression of phospho-JNK and infarct volume in ischemic brain of JIP1-deficient mice.

Mice lacking JIP1, a scaffold protein that organizes JNK pathway components, were constructed independently by two groups. The proposed in vivo function, however, remains contradictory; One study reported that targeted disruption of the jip1 caused embryonic death due to the requirement of JIP1 for fertilized eggs (Thompson et al. [2001] J. Biol. Chem. 276:27745-27748). In contrast, another group (Whitmarsh et al. [2001] Genes Dev. 15:2421-2432) demonstrated that JIP1-deficient mice were viable and that the JIP1 null mutation inhibited the kainic acid-induced JNK activation and neuronal death. The current study was undertaken to re-elucidate the in vivo roles of JIP1 using newly generated JIP1 knockout mice. Our JIP1-deficient mice were viable and healthy. The transient focal ischemic insult produced by middle cerebral artery occlusion (MCAO) strongly activated JNK in brain of jip1(+/+), jip1(+/-), and jip1(-/-) mice. Increased JNK activity was sustained for more than 22 hr in jip1(+/+) and jip1(+/-), whereas it was repressed rapidly in jip1(-/-). Concomitantly, the infarct volume produced by the ischemic insult in jip1(-/-) was reduced notably compared to that in jip1(+/+) brain. These results suggest that JIP1 plays a pivotal role in regulating the maintenance of phosphorylated JNK and neuronal survival in postischemic brain, but is not essential for JNK activation and early development.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Preparation of (188) Re-labeled paper for treating skin cancer.

For homogeneous delivery of beta radiation to skin cancer, we developed a simple method for preparing (188) Re-labeled nitrocellulose paper. The homogeneity and stability of the labeled paper were investigated. Absorbed dose estimates were calculated using the Monte-Carlo method. A 74-MBq (188) Re-labeled paper with 1-cm diameter delivered 147.2 Gy up to 1-mm depth after 2-h irradiation. Animal experiments on tumor-bearing mice showed that 50 Gy is an adequate dose for treating skin cancer. Tumors disappeared 7 days after irradiation in all the groups irradiated by 50 or 100 Gy. The (188) Re-labeled paper provided a convenient, economical, effective, and non-invasive method of treating skin cancer.

Animals↗

PubMed2002

Cationic complex: (99m)Tc-N,N'-dimethyldiaminedithiol.

Diaminedithiol (DADT) or N-monosubstituted DADT is known to form lipophilic neutral chelates with technetium. As a result, they are used for brain imaging agents. However, 99mTc-N,N'-dimethylDADT has been demonstrated to have a positive charge and a lower lipophilicity (log P = 0.1) in this experiment. The results of a biodistribution study showed that most activity was found in the intestine after 1 hr, which is the evidence of bile excretion. Increased heart-uptake in mice suggests that this compound or its derivatives can be used as a myocardial-imaging agent.

Animals↗

PubMedDate not supplied

MR imaging of orbital inflammatory pseudotumors with extraorbital extension.

OBJECTIVE: To demonstrate a variety of MR imaging findings of orbital inflammatory pseudotumors with extraorbital extension. MATERIALS AND METHODS: We retrospectively reviewed the MR features of five patients, who were diagnosed clinically and radiologically as having an orbital inflammatory pseudotumor with extraorbital extension. RESULTS: The types of orbital pseudotumors were a mass in the orbital apex (n = 3), diffuse form (n = 2), and myositis (n = 1). The extraorbital extension of the orbital pseudotumor passed through the superior orbital fissure in all cases, through the inferior orbital fissure in two cases, and through the optic canal in one case. The orbital lesions extended into the following areas: the cavernous sinus (n = 4), the middle cranial fossa (n = 4), Meckel's cave (n = 2), the petrous apex (n = 2), the clivus (n = 2), the pterygopalatine fossa and infratemporal fossa (n = 2), the foramen rotundum (n = 1), the paranasal sinus (n = 1), and the infraorbital foramen (n = 1). On MR imaging, the lesions appeared as an isosignal intensity with gray matter on the T1-weighted images, as a low signal intensity on the T2-weighted images and showed a marked enhancement on the post-gadoliniumdiethylene triamine pentaacetic acid (post-Gd-DTPA) T1-sequences. The symptoms of all of the patients improved when they were given high doses of steroids. Three of the five patients experienced a recurrence. CONCLUSION: MR imaging is useful for demonstrating the presence of a variety of extraorbital extensions of orbital inflammatory pseudotumors.

Adult↗