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Biomedical subjects

Jong-Min Kim

Publications and source records attributed to Jong-Min Kim.

At least 19 recordsLinked to original sources

Serum amyloid A induces WISH cell apoptosis.

AIM: Serum amyloid A (SAA) is an important mammalian acute reactant. Here, we aim to investigate the effect of SAA on apoptosis and its mechanism of action in human amniotic WISH cells. METHODS: The expression of formyl peptide receptor (FPRL1), which is reported as a SAA receptor, was tested using RT-PCR and ligand binding assay with radio-labeled FPRL1 ligand. The effect of SAA on proliferating cell population was evaluated by thymidine incorporation assay. The protein phosphorylation levels and caspase-3 activity were detected by Western blot assay. RESULTS: SAA inhibits thymidine incorporation in human amniotic WISH cells. A SAA-induced decrease of proliferating cell population was accompanied with nuclear condensation and caspase-3 activation in WISH cells, suggesting that SAA induces WISH cell apoptosis. Since FPRL1 has been reported as a SAA receptor, we investigated the effects of several FRPL1 agonists on a proliferating cell population in WISH cells. Among the tested FPRL1 agonists, only SAA induced a decrease of proliferating cell population in WISH cells. On the downstream signaling of SAA, we found that SAA stimulated extracellular signal-regulated kinase and p38 kinase, which were not inhibited by pertussis toxin (PTX), ruling out the role of PTX-sensitive G-proteins. Furthermore a SAAinduced decrease of proliferating cell population was not affected by PTX, suggesting that SAA inhibits WISH cell apoptosis in a PTX-sensitive G-proteinindependent manner. A SAA-induced decrease of a proliferating cell population was completely blocked by PD98059 and SB203580, suggesting that mitogenactivated protein kinase activities are essentially required for the process. CONCLUSION: SAA is a novel inducer for WISH cell apoptosis, and the PTX-insensitive pathway is involved in the process.

Amnion↗

zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells.

In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD-fmk), at usual dosage could not prevent genistein-induced apoptosis of p815 mastocytoma cells. This study was undertaken to reveal the mechanism underlying the incapability of zVAD-fmk in preventing this type of apoptosis. We observed that 14-3-3 protein level was reduced in genistein-treated cells and that BocD-fmk but not zVAD-fmk prevented the reduction of 14-3-3 protein level and the release of Bad from 14-3-3. We also demonstrated that truncated Bad to Bcl-xL interaction in genistein- treated cells was prevented by BocD-fmk but not by zVAD-fmk treatment. Our data indicate that BocD- fmk, compared to zVAD-fmk, has a certain preference for inhibiting 14-3-3/Bad signalling pathway. We also elucidated that this differential efficacy of BocD-fmk and zVAD-fmk resulted from the different effect in inhibiting caspase-6 and that co-treatment of zVAD-fmk and caspase-6 specific inhibitor substantially prevented genistein-induced apoptosis. Our data shows that caspase-6 plays a role on Bad/14-3-3 pathway in genistein-induced apoptosis of p815 cells, and that the usual dose of zVAD-fmk, in contrast to BocD-fmk, did not prevent caspase-6 acting on 14-3-3/Bad-mediated event.

14-3-3 Proteins↗

Nuclear interaction of Smac/DIABLO with Survivin at G2/M arrest prompts docetaxel-induced apoptosis in DU145 prostate cancer cells.

Smac/DIABLO is released by mitochondria in response to apoptotic stimuli and is thought to antagonize the function of inhibitors of apoptosis proteins. Recently, it has been shown that, like XIAP, Survivin can potentially interact with Smac/DIABLO. However, the precise mechanisms and cellular location of their action have not been determined. We report for the first time that Smac/DIABLO translocates to the nucleus and is colocalized with Survivin at mitotic spindles during apoptosis resulting from G2/M arrest due to docetaxel treatment of DU145 prostate cancer cells. Our data demonstrate that the nuclear interaction of Smac/DIABLO with Survivin is an important step for suppressing the anti-apoptotic function of Survivin in Doc-induced apoptosis. This suggests that the balance between cellular Smac/DIABLO and Survivin levels could be critical for cellular destiny in taxane-treated cancer cells.

Antineoplastic Agents↗

Development of ligand-dependent regulatory system and its application to gene therapy of insulin-dependent diabetes mellitus.

To develop an inducible expression system, the enhanced artificial nuclear receptors and target reporters were constructed. Artificial nuclear receptors were generated by fusing three domains, consisting of DNA-binding domain (DBD) of GAL4, ligand binding domain (LBD) of progesterone or estrogen receptor, and activation domain (AD) of VP16, sterol regulatory element binding protein (SREBP)-1a, or SREBP-2. The activation domain of SREBP-1a showed most potent transcriptional activity. The maximal level of target reporter gene expression was extremely elevated by the usage of ATP citrate-lyase (ACL) minimal promoter -60/+67 in place of artificial TATA promoter, while the SV40 enhancer severely increased the basal transcription in the absence of ligand. The induction system, developed in the present study, was applied to cell therapy, resulting in successful induction of single-chain insulin analogue (SIA) gene expression to correct the hyperglycemia in diabetic animals. By means of subcutaneous cell therapy, the SIA gene expression rapidly occurred after the local topical application of ligand. These results suggest that our system represents a powerful tool for transcriptional regulation of target gene that can be used for diverse applications, ranging from basic research to gene therapy.

Animals↗

Arthroscopic synovectomy of the knee joint in rheumatoid arthritis: surgical steps for complete synovectomy.

For successful arthroscopic total synovectomy in rheumatoid arthritis of the knee, proper sequential steps are required. First, we resect hypertrophied synovial villi on the intercondylar notch to make a gateway for the posterior compartments. We also perform synovectomy at the posterolateral chamber because of the narrower space of the chamber than that of the posteromedial chamber and the intra-articular crowding due to swollen synovial villi with the passage of operation time. Special care should be taken not to overlook both posterior back corners and roofs, which cannot be seen through the transnotch view, even with a 70 degrees arthroscope. The posterior back corners and roofs can be visualized by using the trans-septal approach technique. In this approach, we prefer to perforate the posterior septum in the posterolateral-to-posteromedial direction to avoid damaging the neurovascular structures because the structures are located just behind and lateral to the midline septum and the posteromedial capsule bulges a bit more posteriorly than the posterolateral capsule. Attention is then directed to the medial, lateral, and suprapatellar compartments, and finally the retropatellar compartment. Our surgical steps are safe and effective for complete synovectomy of the rheumatoid arthritic knee joint and other synovial disorders.

Arthritis, Rheumatoid↗

Meniscal allograft transplantation after total meniscectomy of torn discoid lateral meniscus.

PURPOSE: The purpose of this study was to evaluate the short- to intermediate-term results of meniscal allograft transplantation after total meniscectomy of torn discoid lateral menisci, which are usually wider and thicker than normal lateral menisci. METHODS: Between 1996 and 2003, 14 meniscal allografts were implanted in 14 patients with a previous total or near-total resection of torn discoid lateral menisci. All patients had a minimum of 21 months of follow-up, with a mean of 58 months. Osteochondritis dissecans was present in 3 cases, and osteochondral autograft transfer was performed in those cases. All patients were evaluated with the modified Lysholm scoring system. Postoperative magnetic resonance imaging was performed in 13 cases, and second-look arthroscopy was performed in 6. RESULTS: Symptoms improved in all cases, and the modified Lysholm score increased on average from 71.4 preoperatively to 91.4 postoperatively. Postoperative magnetic resonance imaging showed secure integration of meniscal allograft in general. The 6 second-look arthroscopies revealed 4 normal menisci, 1 meniscus with anterior horn shrinkage, and 1 meniscus with a tear at the posterior horn of the allograft. CONCLUSIONS: The short- to intermediate-term results confirmed noteworthy clinical improvements and consistent objective findings. Meniscal allograft transplantation after total meniscectomy of torn discoid lateral menisci could be a reasonable treatment option in symptomatic patients. Nevertheless, long-term observation would be required to evaluate the longevity of these results. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Activities of Daily Living↗

Oro-bucco-lingual dyskinesia associated with nonketotic hyperglycaemia.

Nonketotic hyperglycaemia is typically associated with a hemiballism-hemichorea pattern of involuntary movement and is characterized by hyperintense signal within the contralateral striatum on T(1)-weighted magnetic resonance imaging (MRI). An oro-bucco-lingual syndrome and location of the lesions has not been previously described. Herein, we report a patient with oro-bucco-lingual dyskinesia associated with nonketotic hyperglycaemia. MRI revealed characteristic T(1) hyperintense lesions in the bilateral putamen.

Aged↗

Arthroscopic synovectomy in wrists with advanced rheumatoid arthritis.

UNLABELLED: We evaluated the effects of arthroscopic wrist synovectomy for patients with advanced rheumatoid arthritis. We retrospectively reviewed data for 11 patients with moderately advanced arthritis and joint space narrowing of 25% to 50% (Group A) treated from May 1993 to March 2000. We compared effects of these patients with effects of six patients with earlier disease and joint space narrowing of 0% to 25% (Group B). For Group A, the total modified Mayo wrist scores increased from an average of 26.36 points preoperatively to an average of 56.36 points postoperatively. Postoperative scores for pain and return to work status, and two components of the modified Mayo wrist score also showed differences compared with the respective preoperative scores. There was an increase in final followup scores in return to work status and total modified Mayo wrist scores. Group A showed larger differences than Group B. Our data suggest that arthroscopic synovectomy is a useful treatment for modest and moderate stages of rheumatoid arthritis. It is especially effective for decreasing pain and improving function, allowing patients to return to work. LEVEL OF EVIDENCE: Therapeutic study, Level III. See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗

Pyruvate protects motor neurons expressing mutant superoxide dismutase 1 against copper toxicity.

Mutations in the copper/zinc superoxide dismutase (SOD1) gene are known to be responsible for familial amyotrophic lateral sclerosis. Alteration of metal binding properties of mutant SOD1 has been proposed to play a role in the pathogenesis of amyotrophic lateral sclerosis. We investigated the toxic effects of excess extracellular copper on motor neuronal cells expressing human mutant SOD1 (G93A), and evaluated the neuroprotective effects of energy metabolism intermediates or cofactors. Motoneuron-neuroblastoma hybrid (VSC 4.1) cells expressing mutant SOD1, when treated with copper chloride, showed reduced viability and increased levels of endogenous peroxides. Moreover, this copper-induced toxicity was attenuated by a free radical scavenger, a caspase inhibitor, or a calpain inhibitor. Of the energy metabolism intermediates examined, pyruvate significantly reduced the death and production of reactive oxygen species in cells expressing mutant SOD1. Our data suggest that pyruvate could be of therapeutic value in some forms of familial amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗

Ferrous and ferric iron accumulates in the brain of aged Long-Evans Cinnamon rats, an animal model of Wilson's disease.

The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper (Cu) in its liver, is an animal model of Wilson's disease. We evaluated and compared the distributions of Cu, ferrous (Fe2+), and ferric (Fe3+) iron in four-brain regions, namely, in the cerebral cortex, cerebellum, substantia nigra (SN), and striatum of LEC and Long-Evans Agouti rats at 30 and 55 weeks. Cu levels were elevated in the striatum of LEC rats, and Fe2+ and Fe3+ were higher in the striatum and SN of LEC rats. Ratios of Fe2+ to Fe3+ were > 1 in four regions, and were highest in the striatum and SN of LEC rats. Cu and iron levels were found to be augmented during aging, and we suggest that these accumulations may exert deleterious effects in aged LEC rats. This study is the first report that demonstrates regional differences of Fe2+ and Fe3+ accumulation in the brain of aged LEC rats. Further studies are required to elucidate the mechanisms of Cu and iron accumulations and of their effects.

Aging↗

Arthroscopic all-inside repair of tears of the anterior horn of the lateral meniscus.

Presently, the outside-in or inside-out meniscal repair techniques are recommended for the repair of tears of the anterior horn of the lateral meniscus. However, an incision about 1 to 2 cm or more in length is needed, and the biomechanics of the lateral meniscus may be altered during motion. We have developed a new alternative repair technique to prevent this skin incision and preserve the normal biomechanics of the lateral meniscus during motion. We use 3 portals: a lateral patellofemoral axillary portal, a standard anterolateral portal, and an extreme far medial portal. We perform all-inside repair for tears of the anterior horn of the lateral meniscus using suture hooks.

Adult↗

Alternative usages of multiple promoters of the acetyl-CoA carboxylase beta gene are related to differential transcriptional regulation in human and rodent tissues.

Acetyl-CoA carboxylase beta (ACCbeta) is a critical enzyme in the regulation of fatty acid oxidation and is dominantly expressed in the skeletal muscle, heart, and liver. It has been established that two promoters, P-I and P-II, control the transcription of the ACCbeta gene. However, the precise mechanism involved in controlling tissue-specific gene expression of ACCbeta is largely unknown yet. In this study we revealed that promoter P-I, active in the skeletal muscle and heart but not in the liver, could be activated by myogenic regulatory factors and retinoid X receptors in a synergistic manner. Moreover, P-I was also activated markedly by the cardiac-specific transcription factors, Csx/Nkx2.5 and GATA4. These results suggest that the proper stimulation of P-I by these tissue-specific transcription factors is important for the expression of ACCbeta according to the tissue types. In addition, CpG sites around human exon 1a transcribed by P-I are half-methylated in muscle but completely methylated in the liver, where P-I is absolutely inactive. In humans, the skeletal muscle uses P-II as well as P-I, whereas only P-I is active in rat skeletal muscle. The proximal myogenic regulatory factor-binding sites in human P-II, which are not conserved in rat P-II, might contribute to this difference in P-II usage between human and rat skeletal muscle. Hepatoma-derived cell lines primarily use another novel promoter located about 3 kilobases upstream of P-I, designated as P-O. This study is the first to explain the mechanisms underlying the differential regulation of ACCbeta gene expression between tissues in living organisms.

5' Untranslated Regions↗

Controlled transcriptional regulation in eukaryotes by a novel transcription factor derived from Escherichia coli purine repressor.

Unlike the DNA-binding domains (DBD) of most eukaryotic transcription factors, Escherichia coli LacI family transcription factors are unable to bind to specific target DNA sequences without a cofactor-binding domain. In the present study, we reconstructed a novel DBD designated as PurHG, which binds constitutively to a 16bp purine repressor operator, by fusion of the purine repressor (PurR) DBD (residues 1-57) and the GAL4 dimerization domain (DD, residues 42-148). Binding of PurHG to DNA requires the dimerization and a hinge helix of PurR DBD. When the PurHG was expressed as a fusion protein in a form of a transcription activator (PurAD) or an artificial nuclear receptor (PurAPR or PurAER) responding to ligand, such as RU486 or beta-estradiol, it could regulate the expression of the reporter genes in NIH3T3 cells. The prerequisite region of the GAL4 DD for DNA-binding was amino acid residues from 42 to 98 in the form of PurAD, while the amino acid residues from 42 to 75 were sufficient for ligand-dependent regulation in the form of PurAPR. These results suggest that the dimerization function of the progesterone ligand-binding domain could be substituted for region 76-98 of the GAL4 DD. In summary, the fusion of the PurR DBD and the GAL4 DD generates fully active DNA-binding protein, PurHG, in vitro and in vivo, and these results provide the direct evidence of structural predictions that the proximate positioning of PurR hinge helical regions is critical for DNA-binding.

Base Sequence↗

TRAIL induces apoptosis of chondrocytes and influences the pathogenesis of experimentally induced rat osteoarthritis.

OBJECTIVE: To investigate whether TRAIL influences the pathogenesis of osteoarthritis (OA). METHODS: A recombinant adenoviral vector system (Ad-TRAIL) was used. Expression of TRAIL in a rat chondrocyte cell line (RCJ3.1C.18) and alterations in the expression of death and decoy receptors after Ad-TRAIL infection were measured by Western blot assay. To explore the underlying mechanism, Western blot assays (to detect caspase 8, poly[ADP-ribose] polymerase [PARP], and caspase 3 activation), mitochondrial membrane potential (DeltaPsim) measurement, Hoechst staining, and DNA electrophoresis were conducted. Next, expression of TRAIL and death and decoy receptors was examined by immunochemistry in primary cultured chondrocytes and on cartilage obtained from rats with experimentally induced OA. RESULTS: Ad-TRAIL infection induced expression of TRAIL in RCJ3.1C.18 cells, increased expression of death receptor 4 (DR4), and decreased expression of DR5 and decoy receptor 1 (DcR1). Ad-TRAIL, at doses of 10 and 100 multiplicities of infection, decreased the viability of chondrocytes 4 days after infection. Reduction of DeltaPsim, cytochrome c release, nuclear condensation, activation of caspase 3 and PARP, and DNA fragmentation proved the induction of apoptosis. Activation of caspase 8 was also observed. Ad-TRAIL also induced apoptosis in primary cultured chondrocytes, in which alterations in expression of TRAIL and death receptors were similar to those observed in RCJ3.1C.18 cells. Cartilage obtained from rats with experimentally induced OA showed increased expression of TRAIL and DR4 and decreased expression of DR5 and DcR1 compared with control cartilage. CONCLUSION: TRAIL induces chondrocyte apoptosis, and TRAIL-induced chondrocyte apoptosis may play a role in the pathogenesis of OA.

Animals↗

Investigation of common mitochondrial point mutations in Korea.

Between 1997 and 2002, 65 patients with suspected mitochondrial diseases were screened for the mitochondrial point mutations A3243G, T3271C, A8344G, and T8356C. Among these patients, 15 were found to have one of these mutations: 12 with A3243G and 3 with A8344G. The phenotypes of A3243G and A8344G mutations were MELAS and MERRF, respectively. Many asymptomatic family members had the same mutations. In this report, detailed clinical and laboratory findings are presented.

Adolescent↗

The ultrasonographic and electrodiagnostic findings of ulnar neuropathy at the elbow.

OBJECTIVE: To evaluate and compare the morphologic changes of the ulnar nerve at the elbow, using ultrasonography, between patients with cubital tunnel syndrome and retrocondylar compression syndrome determined with electrodiagnosis. DESIGN: Prospective study using electrodiagnosis and ultrasonography. SETTING: An outpatient rehabilitation clinic in a tertiary university hospital in South Korea. PARTICIPANTS: Thirteen patients (8 men, 5 women; mean age, 48.2y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: In the electrodiagnostic study, we used the inching technique to localize the ulnar nerve lesion at the elbow. In the ultrasonography study, we measured the length of the swollen ulnar nerve and the ratio of the nerve diameter between the proximal end of the medial epicondyle to the elbow joint level and the tip of medial epicondyle to the elbow joint level. RESULTS: The mean length of the swollen ulnar nerve segment in retrocondylar compression syndrome (2.58+/-0.58cm) was significantly longer than that of cubital tunnel syndrome (1.64+/-0.31cm). The mean ratio of the nerve diameter between the proximal end of medial epicondyle and the elbow joint level was significantly larger in retrocondylar compression syndrome (1.52+/-0.25) than that of cubital tunnel syndrome (1.06+/-0.06). CONCLUSIONS: Ultrasonography detected the morphologic changes and the extent of the ulnar nerve lesion at the elbow, and it can become a screening and follow-up imaging modality in patients with ulnar neuropathy at the elbow.

Elbow Joint↗

Radial tears of the posterior horn of the medial meniscus.

PURPOSE: The purpose of this study was to introduce clinical features and characteristics of radial tears of the posterior horn of the medial meniscus and the results of arthroscopic surgery. TYPE OF STUDY: Retrospective case series. METHODS: From August 1996 to December 1999, 345 consecutive cases of medial meniscal tears were treated using arthroscopic surgery in Asan Medical Center, Seoul, Korea. Of these, 96 cases (27.8%) with radial tears of the posterior horn of the medial meniscus were reviewed. All patients were treated with arthroscopic partial meniscectomy. Based on medical records, including surgical notes and detailed arthroscopic photographs, we reviewed the age distribution of the patients, preoperative physical signs, magnetic resonance imaging, surgical findings, and clinical results using the Lysholm Knee Scoring scale and our own questionnaire. RESULTS: Radial tears of the posterior horn of the medial meniscus were more common than previously known and also were more common in elderly patients. Most patients presented mechanical symptoms. Magnetic resonance imaging often failed to reveal the tears. Careful attention to the nature of pain and the physical examination was critical in making a diagnosis. Although most patients were elderly and had degenerated articular cartilages, subjective symptoms improved significantly after arthroscopic partial meniscectomy. CONCLUSIONS: Radial tears of the medial meniscus posterior horn are common. Diagnosis of this tear is often difficult because most patients have osteoarthritic knees masking meniscal tears and magnetic resonance imaging shows unacceptably high rates of false-negative results. Following strict surgical indications, arthroscopic partial meniscectomy can help patients with low morbidity. LEVEL OF EVIDENCE: Level IV therapeutic study (case series, no or historical control group).

Adult↗

A case of adult onset tic disorder following carbon monoxide intoxication.

BACKGROUND: Adult onset tic disorders are usually secondary in origin. We report a case of adult onset tic disorder following carbon monoxide (CO) intoxication with typical magnetic resonance imaging features. CASE REPORT: A 36-year-old woman developed temporarily suppressible patterned movements on her face, neck, and shoulder associated with sensory discomfort after CO poisoning. Magnetic resonance images showed bilateral symmetric cavitary changes in the globus pallidus. Clonazepam relieved much of her symptoms. CONCLUSION: Our patient developed a monosymptomatic tic disorder following CO intoxication. This further supports that altered outflow signals from the basal ganglia, especially the globus pallidus, may contribute to the development of tic disorders.

Adult↗