Biomedical subjects

K M Kim

Publications and source records attributed to K M Kim.

At least 37 records · Page 2Linked to original sources

PubMed2001

Post-translational modification of the N-terminal His tag interferes with the crystallization of the wild-type and mutant SH3 domains from chicken src tyrosine kinase.

Structural studies of the wild type and mutants of the src SH3 domain were initiated to elucidate the correlation of the native-state topology with protein thermostability and folding kinetics. An extra mass of 178 Da arising from the post-translational modification at the N-terminal His tag was observed. The spontaneous alpha-N-6 gluconoylation at the amino group of the His-tagged SH3 domain contributed to the observed extra mass. The partial modification of the N-terminal His-tag produced heterogeneity, both in size and in charge, in the Escherichia coli expressed SH3 domain. The removal of the His tag from the SH3 domain was essential for the crystallization of both wild-type and mutant src SH3. Both the wild type and the W43I mutant were crystallized by hanging-drop vapor diffusion and are in the hexagonal space group P6(5)22 with one molecule in the asymmetric unit. Data sets were collected to 1.8 and 1.95 A resolution for the the wild type and the W43I mutant, respectively.

Amino Acid Sequence↗

PubMed2001

Differential regulation of NO availability from macrophages and endothelial cells by the garlic component S-allyl cysteine.

Garlic has been used as a traditional medicine for prevention and treatment of cardiovascular diseases. However, the molecular mechanism of garlic's pharmacological action has not been clearly elucidated. We examined here the effect of garlic extract and its major component, S-allyl cysteine (SAC), on nitric oxide (NO) production by macrophages and endothelial cells. The present study demonstrates that these reagents inhibited NO production through the suppression of iNOS mRNA and protein expression in the murine macrophage cell line RAW264.7, which had been stimulated with LPS and IFNgamma. The garlic extract also inhibited NO production in peritoneal macrophages, rat hepatocytes, and rat aortic smooth muscle cells stimulated with LPS plus cytokines, but it did not inhibit NO production in iNOS-transfected AKN-1 cells or iNOS enzyme activity. These reagents suppressed NF-kappaB activation and murine iNOS promoter activity in LPS and IFNgamma-stimulated RAW264.7 cells. In contrast, these reagents significantly increased cGMP production by eNOS in HUVEC without changes in activity, protein levels, and cellular distribution of eNOS. Finally, garlic extract and SAC both suppressed the production of hydroxyl radical, confirming their antioxidant activity. These data demonstrate that garlic extract and SAC, due to their antioxidant activity, differentially regulate NO production by inhibiting iNOS expression in macrophages while increasing NO in endothelial cells. Thus, this selective regulation may contribute to the anti-inflammatory effect and prevention of atherosclerosis by these reagents.

Animals↗

PubMed2001

Quantitative trait loci mapping associated with plant regeneration ability from seed derived calli in rice (Oryza sativa L.).

Quantitative trait loci (QTLs), which are associated with the ability of plant regeneration from seed derived calli, were detected using a recombinant inbred (RI) population from a cross between 'Milyang 23 (toingil)' and 'Gihobyeo (japonica)' in rice (Oryza sativa L.). A tongil type cultivar, 'Milyang 23', has a lower frequency of callus induction and plant regeneration than those of japonica 'Gihobyeo'. Transgressive segregations were observed for the callus induction rate and plant regeneration ability from seed derived calli of the RI population. An interval mapping analysis was used to identify the QTL controlling the plant regeneration ability. Two QTLs for the callus induction rate were detected on chromosomes 1 and 2, explaining the 10.9% total phenotypic variation. Four QTLs that are associated with the plant regeneration ability were located on chromosomes 2, 3, and 11, accounting for 25.7% of the total phenotypic variation.

Chromosome Mapping↗

PubMed2001

Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma.

Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.

Humans↗

PubMed2001

Cellular mechanism of calcification and its prevention in glutaraldehyde treated vascular tissue.

OBJECTIVES: Prevention of calcification in glutaraldehyde (GA) treated porcine aortic valve fibroblasts and rat aorta with Ca2+ channel blockers (Ca(2+)-CBs). BACKGROUND: GA causes a massive increase in [Ca2+]i and a many fold increase in [Pi]i followed by calcification of porcine aortic valve fibroblasts. The influx of extracellular Ca2+ into [Pi]i rich cells apparently underlies the mechanism of calcification. Inhibition of Ca2+ influx is likely to prevent calcification in GA-treated cells. METHODS: [Ca2+]i in GA-treated cells was measured by fluorescence image analysis. [Ca2+]i increase in fibroblasts treated with various Ca(2+)-CBs was compared with the untreated control. To study the role of Ca2+ influx in calcification and to find out the portals of Ca2+ entry, porcine aortic valve fibroblasts and freshly removed rat aorta were treated with verapamil + ryanodine, or verapamil + econazole, fixed with GA and incubated in Hank's balanced salt solution with 2.5 mmol/L calcium. The progress of calcification was monitored by the rate of Ca and Pi depletions from the supernatant. Calcified cells and tissues were identified by calcein fluorescence. RESULTS: Verapamil + ryanodine or econazole inhibited the GA-induced Ca2+ influx and prevented calcification of the cells and rat aorta. The effect of verapamil was additive to that of ryanodine and econazole. CONCLUSIONS: Findings further support the influx theory of calcification. Ca2+ enters GA-treated cells mainly through the store operated and the L-type Ca2+ channels. Ca(2+)-CBs may be useful for prevention of calcification in GA-treated vascular bioprostheses. Cell culture serves as a convenient model for screening drug effects on calcification.

Animals↗

PubMed2001

Evidence for two modes of allelic loss: multifocal analysis on both early and advanced gastric carcinomas.

To assess the extent and the timing of allelic loss required for the progression of gastric carcinoma, the intratumoral distribution of loss of heterozygosity (LOH) was compared in early and advanced tumors: early loss is uniformly observed in all tumor areas and late loss is localized in parts of tumor tissue. Tumor sites (167 sites) obtained from 42 gastric carcinoma tissues (26 advanced cancers and 16 early cancers) were examined for LOH on chromosomes 5q, 9p, 13q, 17p, and 18q. By using two or three microsatellite markers for each chromosome arm, it was shown that of 29 tumors showing LOH in at least one tumor site, 15 (51.7%, 12 advanced and three early cancers) harbored multiple losses on three or more chromosome arms, and 89.4% (84 of 94) of these losses was uniformly found in all tumor sites tested. In the remaining 14 tumors (48.3%, eight advanced and six early tumors) with sporadic losses on one or two chromosome arms, 44% (11 of 25) of the losses were commonly shared among the sites tested. Such marked difference (P<0.001, Fisher's exact test) in the intratumoral distribution of multiple and sporadic LOH patterns proposes two distinct LOH subtypes: multiple losses (high LOH), occurring at an early stage with a few additional losses, and sporadic losses (low LOH), taking place relatively late during tumor progression. The multifocal LOH findings imply that, rather than being gradual, the allelic losses take place in two manners that are already determined at an early stage.

Alleles↗

PubMed2001

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.

Adolescent↗

PubMed2001

Phase I/II trial of docetaxel and vinorelbine in patients with non-small cell lung cancer previously treated with platinum-based chemotherapy.

We conducted a phase I/II trial of the combination of docetaxel and weekly vinorelbine in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) who were refractory or resistant to platinum-based regimens. The objectives of the study were (1) to determine the maximum tolerated doses of docetaxel and weekly vinorelbine when given in combination and (2) to evaluate the response to and quantitative and qualitative toxicity of this combination of agents. Patients were required to have an ECOG performance status of 0 or 1, evaluable lesions, and no prior treatment with docetaxel or vinorelbine. A total of 30 patients were treated on this phase I/II study. Eight patients were treated at various doses on the phase I portion of the study. Twenty-two patients (11 males, 11 females, median age 64.5 years) were treated at the phase II dose of vinorelbine 15 mg/m(2) weekly with docetaxel 60 mg/m(2) on day 1 of a 21 day cycle. Twenty of these 22 patients enrolled at the phase II dose required dose modification or delay. Sixteen patients experienced absolute neutrophil count (ANC) <500/mm(3), and eight patients had neutropenic fever. Four patients experienced partial response (18%), nine patients had stable disease (41%), and nine patients had progressive disease (41%). With a median follow-up of 11 months, median survival for these 22 patients was 15.9 months (95% CI 8.1, 23.6 months). Median time to disease progression was 3.2 months with a 95% CI of (1.4, 4.1) months. Thus, the combination of docetaxel 60 mg/m(2) every 3 weeks and vinorelbine 15 mg/m(2) weekly appears to be active as a second line regimen in NSCLC, although it is a highly myelosuppressive regimen requiring dose modification in 91% of patients.

Adult↗

PubMed2001

Graphical search for two-stage designs for phase II clinical trials.

In a typical two-stage design employed in a phase II cancer clinical trial for efficacy screening, a fixed number of patients are initially enrolled. The trial may be terminated for lack of clinical efficacy of treatment if the observed number of treatment successes after the first stage is too small. Otherwise, an additional fixed number of patients are enrolled to accumulate additional information on efficacy. Simon's optimal design and minimax design have often been applied to designing phase II clinical trials. Other designs have largely been ignored. In this paper, we introduce a graphical method to search for a good design that is a compromise between the optimal and the minimax designs.

Clinical Trials, Phase II as Topic↗

PubMed2001

Devising an objective nasal vibration test for nasal resonatory disorders.

The present study investigates the clinical applicability of a new device, which objectively measured nasal resonating vibration via piezoelectric vibratory sensor in 10 normal volunteers, 10 patients with definite hypernasality, and 10 nasal polyposis patients. For the assessment of the hypernasality, the ratio of /ng/ to /a/ as well as the ratio of /mama/ to /papa/ passages were used. For the evaluation of hyponasality, the ratio of nasal vibration postinduced to preinduced cul-de-sac resonation was calculated. The control group showed the ratio of /ng/ to /a/ and /mama/ to /papa/ passages to be larger than 8, whereas the ratio was markedly lower in the hypernasality group. The vibratory signals of /a/ and /ng/ increased markedly in the control and the hypernasality groups after inducing cul-de-sac resonation, but the change was minimal in the hyponasality group. This new device could detect nasal resonatory disorders and readily differentiate between hypernasality and hyponasality.

Humans↗

PubMed2001

Functional characteristics of a new electrolarynx "Evada" having a force sensing resistor sensor.

Electrolarynxes have been used as one of the rehabilitation methods for laryngectomees. Earlier electrolarynxes could not alter frequency and intensity simultaneously during conversation. Recently, we developed an electrolarynx named "Evada" (prototype so far) using a force sensing resistor (FSR) sensor that can control both frequency and intensity simultaneously during conversation. Employing three types of electrolarynxes (Evada, Servox-inton, Nu-vois), this study was undertaken to examine the functional characteristics of Evada for the normal control group and for laryngectomess. Five laryngectomees and five normal adults were asked to express three sentences (declarative sentence, "You stay here.", interrogative sentence, "You stay here?", and imperative sentence, "You! Stay here.") using three types of electrolarynxes. Frequency and intensity changes between the first and last vowels in the three sentences were calculated and analyzed statistically by paired t test. The frequency changes in the interrogative and imperative sentences were more prominent in Evada than in Servox-inton and Nu-vois. The intensity changes in the interrogative and imperative sentences were also more prominent in Evada than in Servox-inton and Nu-vois. Evada controls frequency and/or intensity by having the subject press the control button(s). Therefore, Evada appears to be better at producing intonation and contrastive stress than Nu-vois and Servox-inton.

Equipment Design↗

PubMed2001

Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.

PDZ domain-containing proteins play an important role in the targeting and localization of synaptic membrane proteins. Here, we report an interaction between the PDZ domain-containing protein PICK1 and monoamine neurotransmitter transporters in vitro and in vivo. In dopaminergic neurons, PICK1 colocalizes with the dopamine transporter (DAT) and forms a stable protein complex. Coexpression of PICK1 with DAT in mammalian cells and neurons in culture results in colocalization of the two proteins in a cluster pattern and an enhancement of DAT uptake activity through an increase in the number of plasma membrane DAT. Deletion of the PDZ binding site at the carboxyl terminus of DAT abolishes its association with PICK1 and impairs the localization of the transporter in neurons. These findings indicate a role for PDZ-mediated protein interactions in the localization, expression, and function of monoamine transporters.

Animals↗

PubMed2001

Design of a PC-based multimedia telemedicine system for brain function teleconsultation.

During time-critical brain surgery, the detection of developing cerebral ischemia is particularly important because early therapeutic intervention may reduce the mortality of the patient. The purpose of this system is to provide an efficient means of remote teleconsultation for the early detection of ischemia, particularly when subspecialists are unavailable. The hardware and software design architecture for the multimedia brain function teleconsultation system including the dedicated brain function monitoring system is described. In order to comprehensively support remote teleconsultation, multi-media resources needed for ischemia interpretation were included: EEG signals, CSA, CD-CSA, radiological images, surgical microscope video images and video conferencing. PC-based system integration with standard interfaces and the operability over the Ethernet meet the cost-effectiveness while the modular software was customized with a diverse range of data manipulations and control functions necessary for shared workspace and standard interfaces.

Brain Ischemia↗

PubMed2001

Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3.

The Bcl-2-related survival proteins confer cellular resistance to a wide range of agents. Bcl-xL-expressing hepatocyte cell lines are resistant to tumour necrosis factor and anti-cancer drugs, but are more sensitive than isogenic control cells to antimycin A, an inhibitor of mitochondrial electron transfer. Computational molecular docking analysis predicted that antimycin A interacts with the Bcl-2 homology domain 3 (BH3)-binding hydrophobic groove of Bcl-xL. We demonstrate that antimycin A and a Bak BH3 peptide bind competitively to recombinant Bcl-2. Antimycin A and BH3 peptide both induce mitochondrial swelling and loss of DeltaPsim on addition to mitochondria expressing Bcl-xL. The 2-methoxy derivative of antimycin A3 is inactive as an inhibitor of cellular respiration but still retains toxicity for Bcl-xL+ cells and mitochondria. Finally, antimycin A inhibits the pore-forming activity of Bcl-x L in synthetic liposomes, demonstrating that a small non-peptide ligand can directly inhibit the function of Bcl-2-related proteins.

Adenosine Triphosphate↗

PubMed2001

Cnidicin, a coumarin, from the root of Angelica koreana, inhibits the degranulation of mast cell and the NO generation in RAW 264.7 cells.

Cnidicin (1) and five related coumarins were isolated from the root extract of Angelica koreana (Umbelliferae) as active principles responsible for the inhibitory effect on the degranulation process of cultured mast cells. Cnidicin (1) demonstrated a significant inhibition upon the release of beta-hexosaminidase from the cultured RBL-2H3 cells in a dose dependent manner (IC50 value, 25 microM) and upon the nitric oxide production from the activated RAW264.7 cells (IC50 value, 7.5 microM). In agreement with this, cnidicin inhibited the expression of nitric oxide synthase in RAW264.7 cells.

Animals↗

PubMed2001

Eyebrow incision using tattoo for anterior fossa lesions: technical case reports.

Some Korean women draw tattoo in their eyebrow to cover the scant hair. If a patient has a tattoo in her eyebrow, lesions of anterior cranial fossa can be easily managed with this small eyebrow skin incision through a small unilateral supraorbital craniotomy. By this technique, 7 cases of anterior cranial fossa lesions were successfully treated without any major complications. This leads to less facial scar, less operation time and an earlier return to social adaptation.

Adult↗

PubMed2001

Knowledge and performance of the universal precautions by nursing and medical students in Korea.

BACKGROUND: Like the health care workers, nursing and medical students have to go through clinical practices; accordingly, they run a high risk of being exposed to bloodborne diseases. But there are few studies on the realities of preventive education or measures to be taken after exposure to such diseases. The purpose of this study was to identify a knowledge of universal precautions and their performance in practice among the nursing and medical students in Korea. METHOD: This study was based on survey questionnaires with a total of 714 nursing and medical students for the period between November 2, 1998, and April 30, 2000. RESULTS: The average knowledge level of the universal precautions was 267.8 +/- 21.3 (scores ranged from 150 to 300). The knowledge level of the universal precautions of the nursing students (270.4 +/- 19.4) was higher than that of the medical students (261.0 +/- 24.4; P =.000). The average performance level of the universal precautions was 52.7 +/- 6.2 (scores ranged from 14 to 70). The students of the nursing college showed a higher performance level of the universal precautions (53.2 +/- 5.9; P =.002). The correlation between knowledge and performance of the universal precautions showed a weak and positive correlation (r =.317; P=.000). CONCLUSION: The study demonstrated that the knowledge level of the nursing students about universal precautions was relatively higher than that of medical students. The group that receives education about universal precautions has a higher level of knowledge and performance of the universal precautions than that group that receives no such education. The education about universal precautions is indispensable; it is desirable to raise the relative importance for the curriculum of both nursing and medical colleges.

Cross Infection↗

PubMed2001

Preoperative concurrent chemoradiotherapy for stage IIIA non-small cell lung cancer.

Thirty-one patients with stage IIIA non-small cell lung cancer (NSCLC) were treated with preoperative concurrent chemoradiotherapy (CCRT) followed by surgery. The treatment protocol could not be completed in eight patients. The acute hematologic toxicities of grade III or IV occurred in 48.4%, (15/31) after the first chemotherapy cycle, and in 39.1% (9/23) after the second cycle. The most common non-hematologic toxicity was radiation esophagitis. Surgery was attempted in 23 patients and successful in 22 patients (resection rate = 71.0%. Pathologic complete response and down-staging were achieved in 13.6% (3/22) and 68.2% (15/22). The median survival period, 2-year overall survival, local control and disease-free survival rates of all 31 patients and of 22 patients who underwent surgery were 19 months, 37.2%, 49.1%, 35.5%, and 19 months, 43.2%, 51.8%, 25.6%, respectively. On the basis of our observations, preoperative CCRT followed by surgery for stage IIIA NSCLC has resulted in outcomes comparable with those in previous reports.

Adult↗