Biomedical subjects

Deok Ryong Kim

Publications and source records attributed to Deok Ryong Kim.

14 recordsLinked to original sources

PubMed2006

A 20-year-old woman with Hashimoto's thyroiditis and Evans' syndrome.

Here we report the case of a 20-year-old female patient previously diagnosed with Hashimoto's thyroiditis and overt hypothyroidism, and who had been taking synthetic thyroxine (100 microg/day) for eight months. She experienced intermittent dizziness and generalized weakness, and was diagnosed as having severe autoimmune hemolytic anemia (AIHA). We prescribed prednisolone treatment and continued synthetic thyroxine administration. Two years and five months later, she developed idiopathic thrombocytopenic purpura (ITP) and was diagnosed with Evans' syndrome. Thereafter, laparoscopic splenectomy was performed because her autoimmune hemolytic anemia was refractory and dependent on steroid therapy. The HLA genotypes of the patient were HLA-A*020101/A* 2602, HLA-B*270502/B*5401, HLA-Cw*0102/Cw*020202, HLA-DRB1*0404/DRB1*0405, and HLA-DQB1*0302/DQ B1*0401. Hashimoto's thyroiditis is often associated with other nonendocrine autoimmune diseases, and antithyroid antibodies are frequently observed in Evans' syndrome (coexistence of AIHA and ITP). However, there is no report of Evans' syndrome developing in patients with overt hypothyroidism and Hashimoto's thyroiditis. This case suggests that three autoimmune diseases (AIHA, ITP, and Hashimoto's thyroiditis) might share a common immunogenetic pathway in pathogenesis.

Adult↗

PubMed2006

The expression of ketohexokinase is diminished in human clear cell type of renal cell carcinoma.

For identification and targeting of tumor-associated marker proteins, the proteome of clear cell type of renal cell carcinoma (RCC) and normal kidney tissues was analyzed by 2-DE. Ketohexokinase (also called fructokinase), which catalyzes the phosphorylation of fructose to fructose 1-phosphate, was identified by MALDI-TOF MS and found to be expressed at low rates in the renal tumor tissues. We found a decreased amount of ketohexokinase mRNA in RCC compared to that observed in the normal kidney tissues by Northern blot. The activity of ketohexokinase in 20 clear cell RCC specimens and the 20 corresponding normal kidneys was investigated, and its activity was shown to be approximately 1.4-fold lower in the RCC specimens than in the normal kidney. Ketohexokinase activity in tumor stage pT3 RCC was 1.5-fold lower than in pT1 RCC. The level of ketohexokinase activity in histological grade 3 RCC was 1.8-fold lower than that in grade 1 cancer. In addition, using in situ hybridization, it was revealed that ketohexokinase in the normal kidney tissue was confined to the proximal tubular epithelial cells, while the expression of ketohexokinase in RCC tissues was extremely low. Our research results show that the expression of human ketohexokinase was diminished in clear cell RCC.

Adenocarcinoma, Clear Cell↗

PubMed2006

Disease-specific proteins from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly destroys cartilages or bones at the joints. This inflammatory disorder is initiated by self-attack using own immune system, but the detail of pathological mechanism is unclear. Features of autoantigens leading to autoimmune disease are also under veil although several candidates including type II collagen have been suggested to play a role in pathogenesis. In this report, we tried to identify proteins responding to antibodies purified from RA patients and screen proteins up-regulated or down-regulated in RA using proteomic approach. Fibronectin, semaphorin 7A precursor, growth factor binding protein 7 (GRB7), and immunoglobulin mu chain were specifically associated with antibodies isolated from RA synovial fluids. In addition, some metabolic proteins such as adipocyte fatty acid binding protein, galectin-1 and apolipoprotein A1 precursor were overexpressed in RA synovium. Also, expression of peroxiredoxin 2 was up-regulated in RA. On the contrary, expression of vimentin was severely suppressed in RA synoviocytes. Such findings might give some insights into understanding of pathological mechanism in RA.

Adult↗

PubMed2006

A case of hyperglycemic hyperosmolar state associated with Graves' hyperthyroidism: a case report.

Hyperglycemic hyperosmolar state (HHS) is an acute complication mostly occurring in elderly type 2 diabetes mellitus (DM). Thyrotoxicosis causes dramatic increase of glycogen degradation and/or gluconeogenesis and enhances breakdown of triglycerides. Thus, in general, it augments glucose intolerance in diabetic patients. A 23-yr-old female patient with Graves' disease and type 2 DM, complying with methimazole and insulin injection, had symptoms of nausea, polyuria and generalized weakness. Her serum glucose and osmolarity were 32.7 mM/L, and 321 mosm/kg, respectively. Thyroid function tests revealed that she had more aggravated hyperthyroid status; 0.01 mU/L TSH and 2.78 pM/L free T3 (reference range, 0.17-4.05, 0.31-0.62, respectively) than when she was discharged two weeks before (0.12 mU/L TSH and 1.41 pM/L free T3). Being diagnosed as HHS and refractory Graves' hyperthyroidism, she was treated successfully with intravenous fluids, insulin and high doses of methimazole (90 mg daily). Here, we described the case of a woman with Graves' disease and type 2 DM developing to HHS.

Adult↗

PubMed2005

RshA mimetic peptides inhibiting the transcription driven by a Mycobacterium tuberculosis sigma factor SigH.

SigH, an alternative sigma factor in Mycobacterium tuberculosis, is a central regulator in responses to the oxidative and heat stress. This SigH activity is specifically controlled by an anti-sigma factor RshA during expression of stress-related genes. Thus, the specific interaction (k(on)=1.15x10(5) (M(-1) s(-1)), k(off)=1.7x10(-3) (s(-1)), KD=15 nM, determined in this study) between SigH and RshA is crucial for the survival and pathogenesis of M. tuberculosis. Using phage-display peptide library, we defined three specific regions on RshA responsible for SigH binding. Three RshA mimetic peptides (DAHADHD, AEVWTLL, and CTPETRE) specifically inhibited the transcription initiated by SigH in vitro. One of them (DAHADHD) diminished the extent of binding of RshA to SigH in a dose-dependent manner. The binding affinity (KD) of this peptide to SigH was about 1.2 microM. These findings might provide some insights into the development of new peptide-based drugs for TB.

Amino Acid Sequence↗

PubMed2005

Proteomic changes during the B cell development.

An antibody-secreting B cell is derived from a lymphoid stem cell through a series of developmental stages: progenitor B cell (pro-B cell), precursor B cell (pre-B) cell, immature B cell and mature B cell stage. The gene rearrangement of antigen receptor genes and their expression on the cell surface are crucial regulation steps cells to develop to the next stage. This control mechanism occurs at the sequential manner during the B cell development. Proteomic approach using two-dimensional (2-D) gel electrophoresis and mass spectrometry makes possible to analyze the expression pattern of total proteins at each developmental stage and isolate proteins differentially expressed in B cells. Some transcriptional factors such E2A and Pax5 are expressed at the earlier stages of B cell development and repressed at later developmental stages. RAD52-related protein and chromatin assembly factor 1 are dominantly expressed at early B cells undergoing DNA rearrangement. These comparative analyses of total proteins in each B cell can provide some crucial information to understand the molecular basis of B cell ontogeny.

B-Lymphocytes↗

PubMed2005

A case of hypothyroidism and type 2 diabetes associated with type V hyperlipoproteinemia and eruptive xanthomas.

Primary hypothyroidism and type 2 diabetes are both typically associated with the increased level of triglycerides. To date, there have been only a few case reports of type 2 diabetes patients with both type V hyperlipoproteinemia and eruptive xanthomas, but there have been no reports of hypothyroidism patients associated with eruptive xanthomas. We report here on a case of a 48-yr old female patient who was diagnosed with type 2 diabetes and primary hypothyroidism associated with both type V hyperlipoproteinemia and eruptive xanthomas. We found rouleaux formation of RBCs in peripheral blood smear, elevated TSH, and low free T4 level, and dyslipidemia (total cholesterol 18.1 mM/L, triglyceride 61.64 mM/L, HDL 3.0 mM/L, and LDL 2.54 mM/L). She has taken fenofibrate, levothyroxine, and oral hypoglycemic agent for 4 months. After treatment, both TSH level and lipid concentration returned to normal range, and her yellowish skin nodules have also disappeared.

Diabetes Mellitus, Type 2↗

PubMed2004

Chromatin remodeling facilitates DNA incision in UV-damaged nucleosomes.

The DNA repair machinery must locate and repair DNA damage all over the genome. As nucleosomes inhibit DNA repair in vitro, it has been suggested that chromatin remodeling might be required for efficient repair in vivo. To investigate a possible contribution of nucleosome dynamics and chromatin remodeling to the repair of UV-photoproducts in nucleosomes, we examined the effect of a chromatin remodeling complex on the repair of UV-lesions by Micrococcus luteus UV endonuclease (ML-UV endo) and T4-endonuclease V (T4-endoV) in reconstituted mononucleosomes positioned at one end of a 175-bp long DNA fragment. Repair by ML-UV endo and T4-endoV was inefficient in mononucleosomes compared with naked DNA. However, the human nucleosome remodeling complex, hSWI/SNF, promoted more homogeneous repair by ML-UV endo and T4-endo V in reconstituted nucleosomes. This result suggests that recognition of DNA damage could be facilitated by a fluid state of the chromatin resulting from chromatin remodeling activities.

Animals↗

PubMed2004

Functional characterization of mutant CYP17 genes isolated from a 17 alpha-hydroxylase/17,20-lyase-deficient patient.

CYP17 has a dual enzymatic activity that is necessary for steroid hormone biosynthesis. It catalyzes the 17 alpha-hydroxylation of progesterone or pregnenolone and also removes an acetyl moiety of hydroxy-progesterone or hydroxypregnenolone by its 17,20-lyase activity to produce androstenedione or dehydroepiandrosterone (DHEA), respectively. We previously isolated a compound heterozygous mutant of CYP17 from a Korean female patient: 1-base deletion and 1-base transversion mutation at 1 allele and 3-base deletion mutation at the other allele. Here we tested the functional activities of these 2 mutant CYP17 alleles using a transfection analysis in COS-1 cells with radiolabeled substrates and thin layer chromatography. Both mutant CYP17 genes lost not only 17 alpha-hydroxylation activity, but also 17,20-lyase activity in this assay system. This nonfunctional nature of 2 mutant CYP17 genes explains the clinical manifestation of a patient who had 17 alpha-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗

PubMed2004

Elevated urinary 8-isoprostaglandin F(2alpha) in females with Graves' hyperthyroidism.

In this study, we investigate how oxidative stress alters the urinary F2-isoprostanes' level and we examine the correlation between 8-isoPGF(2alpha) and thyroid hormones in female patients with Graves' hyperthyroidism. We quantitatively determined the concentrations of urinary F2-isoprostanes using gas chromatography-mass spectrometry in the selected ion-monitoring mode. We recruited individuals in the following three groups of subjects for this study: (1) female hyperthyroidism patients (n = 14, 21-71 years), (2) female hypothyroidism patients (n = 16, 16-66 years), and (3) female age-matched normal controls (n = 10, 20-61 years). The average concentration of 8-iso prostaglandin F(2alpha) (8-isoPGF(2alpha)) in hyperthyroidism patients was significantly higher than that in the healthy controls (P < 0.05). The concentration of 8-isoPGF(2alpha) in hypothyroidism patients was similar to that in normal controls. Although the level of 8-isoPGF(2alpha) in two of the patients was slightly elevated, the P value was not significant (NS). Our data suggest that the increased level of urinary 8-isoPGF(2alpha) may reflect possible oxidation injuries in hyperthyroidism patients due to the high level of thyroid hormones. Therefore, the elevated 8-isoPGF(2alpha) in patients could be used as an important biomarker for hyperthyroidism disease.

Adolescent↗

PubMed2003

Amino acid residues in RAG1 responsible for the interaction with RAG2 during the V(D)J recombination process.

The V(D)J recombinase, a complex of RAG1 and RAG2, carries out a gene rearrangement process that is required for the achievement of diverse antigen receptor repertoires during the early developmental stage of lymphocytes. It recognizes a specific site spanning the coding DNA region of antigen receptor genes and produces double-stranded DNA breaks at the board between coding and signal sequences. Two broken DNA ends are joined by a double-stranded break repair system. Both RAG (recombination activation gene) 1 and RAG2 proteins are absolutely required for this process although the catalytic residues of V(D)J recombinase are exclusively located at RAG1 according to recent mutational analyses. In this study we identified some acidic amino acid residues in RAG1 responsible for the interaction with RAG2. Mutation on these residues caused a decrease of cleavage activity in vitro and failure of RAG-RSS DNA synaptic complex formation. This result is complementary to previous reports in which positively charged amino acids in RAG2 play an important role in RAG1 binding.

Amino Acids↗

PubMed2003

Recombination activating gene 1 product alone possesses endonucleolytic activity.

Two lymphoid-specific proteins, RAG1 and RAG2, are required for the initiation of the V(D)J recombination in vitro. The V(D)J cleavage that is mediated by RAG proteins at the border between the coding and signal sequences results in the production of a hairpin at the coding end and a double-stranded break at the signal end. Two hairpin coding ends are re-opened, modified, and sealed; whereas, the signal ends are directly ligated. Here I report that only RAG1 can carry out a distinct endonucleolytic activity in vitro using an oligonucleotide substrate that is tethered by a short single-stranded DNA. The purified RAG1 protein alone formed a nick at the near position to the recombination signal sequence. This endonucleolytic activity was eliminated by immunoprecipitation using the RAG1-specific antibody, and required the 3'-hydroxy group. All of the RAG1 mutants that were incapable of the nick and hairpin formation in the V(D)J cleavage analysis also showed this new endonucleolytic activity. This suggests that the nicking activity that was observed might be functionally different from the nick formation in the V(D)J cleavage.

Animals↗

PubMed2003

Comparative analysis of nuclear proteins of B cells in different developmental stages.

The developmental stage-specific regulation of V(D)J recombination, a gene rearrangement process of antigen receptor gene segments, is tightly controlled in cells. Here we screened proteins uniquely or differentially expressed among three developmentally distinguishable B cells (pro-B, pre-B and mature B cells) using two-dimensional gel electrophoresis and mass spectrometry. Chromatin assembly factor 1 was uniquely expressed in pro-B cells. Purine nucleotide phosphorylase, LCK, E2A and many other unidentified proteins were dominantly present in the nucleus at the early stage of B cell development where the V(D)J recombination process occurs. Also, few proteins including guanidine nucleotide binding proteins were exclusively expressed in pre-B cell. Such findings can provide some information to help understand the developmental regulation of gene rearrangement occurring during B cell development.

Animals↗

PubMed2003

A novel compound heterozygous mutation in the CYP17 (P450 17alpha-hydroxylase) gene leading to 17alpha-hydroxylase/17,20-lyase deficiency.

Mutations in the CYP17 gene impair steroid biosynthesis in the adrenals and gonads and often cause 17alpha-hydroxylase/17,20-lyase deficiency, leading to amenorrhea, sexual infantilism, and hypokalemic low aldosterone hypertension. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20-lyase deficiency have been reported previously. In the present study, we found a novel CYP17 mutation from the molecular analysis of a Korean patient with primary amenorrhea with a 46,XX karyotype, and hypokalemic hypertension. We sequenced all 8 exons of the CYP17 gene that were amplified from patient's genomic DNA using polymerase chain reaction (PCR) and found a compound heterozygous mutation in the CYP17 structural gene; a 1-base deletion and a 1-base transversion (TAC-->AA) at codon 329, leading to the production of a truncated protein (1-417 amino acids), and a 3-base deletion (TCC, either 350-351 or 351-352 codon) in the other allele. Restriction enzyme digestion analysis of patient's and parental DNA showed that the 1-base deletion and the 3-base deletion are inherited from mother and father, respectively. Here we conclude that these novel compound heterozygous mutations might account for the patient's clinical manifestations of 17alpha-hydroxylase/17,20-lyase deficiency.

Adult↗