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Biomedical subjects

K J Park

Publications and source records attributed to K J Park.

At least 19 recordsLinked to original sources

The addition of induction chemotherapy with etoposide, ifosfamide, and cisplatin failed to improve therapeutic outcome of concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer -- single institution retrospective analysis.

Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. We retrospectively compared the treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in concurrent group. Clinicopathologic characteristics including age, weight loss, histologic types, and clinical stage did not show significant differences between two groups except for a higher proportion of patients with ECOG performance status 2 in concurrent group (3% vs. 27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related death from tracheoesophageal fistula in induction group. The response rates after concurrent CRT were 41% for induction group and 54% for concurrent group, which showed no significant difference (p=0.560). With median follow-up of 13 (1-92) months, there was a trend toward an advantage for concurrent group in median progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than 10% weight loss within 6 months was significantly associated with poor survival (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent CRT did not show any advantage over concurrent CRT alone in locally advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Compost biofiltration of ammonia gas from bin composting.

The effects of the manure compost/coconut peels on the ammonia removal efficiency were examined from dairy manure composting mixed with crop residues. The high rapid composting and manure compost biofiltration experiments consisted of three biofilter vessels with one composter. Dairy manure amended with rice hulls and sawdust was composted in 605 L pilot-scale composter using continuous aeration for 19 days. Three pilot-scale manure compost biofilter amended with media bed 500 mm in depth and 300 mm in diameter were built to clean ammonia emission from composter, respectively. The manure compost biofilter media in the three experimental vessels was using a 50:50 by weight mixture of manure compost and coconut peels (MC/CP). The ammonia concentrations at the inlet and outlet biofilter media were measured by boric acid traps as described by Hong et al. [Hong, J.H., Keener, H.M., Elwell, D.L., 1998. Preliminary study of the effect of continuous and intermittent aeration on composting hog manure amended with sawdust. Compost Science and Utilization 6 (3), 74-88]. Results indicated that the mixture of MC/CP performed well as a biofilter media and the ammonia removal efficiency was 100% for the filter depth of 500 mm.

Ammonia↗

Changes in outcome with sphincter preserving surgery for rectal cancer in Korea, 1991-2000.

AIM: To report the clinical and oncological data of patients operated on for rectal cancers 3-5 cm from the AV over a 10 year period, including the Sphincter preservation (SP) rate. METHODS: We reviewed medical records of 304 patients with rectal cancers 3-5 cm from the AV who underwent surgical resection from January 1991 through December 2000. The 10 years were divided into three periods based on the introduction of new surgical techniques, specifically, ultralow anterior resection (ULAR) with double stapling in March 1994 and ULAR with coloanal anastomosis in April 1997. The rates of SP, complications and patient survival during these periods were compared. RESULTS: The SP rate increased significantly over the 10 years, from 16.4% in period I (January 1991-February 1994), to 53.0% in period II (March 1994-March 1997), to 86.5% in period III (April 1997-December 2000) (p<0.001). Over time, the age of the patients increased (p=0.004), the length of the distal resection margin became shorter (p=0.005), and the rate of lymph node metastasis increased (p=0.016). The factors significantly influencing SP were the period (p<0.001) and the distance from the AV (p<0.001). Over time, morbidity did not increase, and overall and disease free survival rates did not decrease. In contrast, the overall survival of N2 cases significantly increased over time (p=0.0492). CONCLUSION: Over 10 years, the SP rate in rectal cancers 3-5 cm from the AV was significantly increased by the introduction of the double stapling and coloanal anastomosis techniques. These surgical methods, however, had no effect on morbidity, disease free survival and overall survival rates.

Adult↗

Propagation of pacemaker activity in the guinea-pig antrum.

Cyclical periods of depolarization (slow waves) underlie peristaltic contractions involved in mixing and emptying of contents in the gastric antrum. Slow waves originate from a myenteric network of interstitial cells of Cajal (ICC-MY). In this study we have visualized the sequence and propagation of Ca(2+) transients associated with pacemaker potentials in the ICC network and longitudinal (LM) and circular muscle (CM) layers of the isolated guinea-pig gastric antrum. Gastric antrum was dissected to reveal the ICC-MY network, loaded with Fluo-4 AM and activity was monitored at 37 degrees C. Ca(2+) waves propagated throughout the ICC-MY network at an average velocity of 3.24 +/- 0.12 mm s(-1) at a frequency of 4.87 +/- 0.16 cycles min(-1) (n= 4). The propagation of the Ca(2+) wave often appeared 'step-like', with separate regions of the network being activated after variable delays. The direction of propagation was highly variable (Delta angle of propagation 44.3 +/- 10.9 deg per cycle) and was not confined to the axes of the longitudinal or circular muscle. Ca(2+) waves appeared to spread out radially from the site of initiation. The initiating Ca(2+) wave in ICC-MY was correlated to secondary Ca(2+) waves in intramuscular interstitial cells of Cajal, ICC-IM, and smooth muscle cells, and the local distortion (contraction) in a field of view. TTX (1 microm) had little effect on slow wave or pacemaker potential activity, but 2-APB (50 microm) blocked all Ca(2+) waves, indicating a pivotal role for intracellular Ca(2+) stores. Nicardipine (2 microm) eliminated the Ca(2+) transient generated by smooth muscle, but did not affect the fast upstroke associated with ICC-MY. These results indicate that slow waves follow a sequence of activation, beginning with the ICC-MY and ICC-IM network, followed later by a sustained Ca(2+) transient in the muscle layers that is responsible for contraction.

Anesthetics, Local↗

Hepatitis C virus core protein potentiates TNF-alpha-induced NF-kappaB activation through TRAF2-IKKbeta-dependent pathway.

Previous work has implicated that the core protein of hepatitis C virus (HCV) may play a modulatory effect on NF-kappaB activation induced by TNF-alpha. However, it is unclear how HCV core protein modulates TNF-alpha-induced NK-kappaB activation. Here we show that overexpression of HCV core protein potentiates NF-kappaB activation induced by TNF-alpha. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates NF-kappaB activation through TRAF2. Moreover, we demonstrate that HCV core protein potentiates TRAF2-mediated NF-kappaB activation via IKKbeta. In addition, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-kappaB induced by TNF-alpha. Thus, these observations indicate that HCV core protein may play an important role in the regulation of the cellular inflammatory and immune responses through NF-kappaB.

Antigens, CD↗

Differential expression of Vibrio vulnificus elastase gene in a growth phase-dependent manner by two different types of promoters.

Elastase activity of Vibrio vulnificus was highly dependent on growth phase, reached a maximum during the stationary phase, and was regulated at the level of transcription. The stationary phase production of elastase in crp or rpoS mutants, which were constructed by allelic exchanges, decreased about 3- and 10-fold, respectively. However, the promoter activity of vvpE encoding elastase was unaffected by those mutations in the log phase when analyzed using a vvpE-lux fusion. A primer extension analysis revealed that the transcription of vvpE begins at two different sites, consisting of putative promoter L (PL) and promoter S (PS). The PL activity was constitutive through the log and stationary phases, lower than the PS activity, and unaffected by the crp or rpoS mutations. The transcription of PS, induced only in the stationary phase, was dependent on RpoS. The mutation in crp reduced the activity of PS; however, the additional inactivation of crp did not influence the PS activity in the rpoS mutant, indicating that CRP exerted its effects through PS requiring RpoS. These results demonstrate that vvpE expression is differentially directed by PL and PS depending on the growth phase and elevated by RpoS and CRP in the stationary phase.

Alleles↗

Hepatitis C virus core protein potentiates c-Jun N-terminal kinase activation through a signaling complex involving TRADD and TRAF2.

The hepatitis C virus (HCV) core protein is a multifunctional viral nucleocapsid protein. Previously, it has been demonstrated that the HCV core protein interacts with the cytoplasmic domain of tumor necrosis factor receptor 1 (TNFR1). Since the TNFR1 is engaged in stimulation of transcriptional factor NF-kappaB and AP-1 through activation of IkappaB kinase and c-Jun N-terminal kinase (JNK, or stress-activated protein kinase), respectively, we have examined whether the interaction between core protein and TNFR1 can modulate JNK. In this study, we demonstrate that the HCV core protein synergistically activates TNFalpha-induced JNK at a core concentration dependent manner in human embryonic kidney (HEK) 293 cells. HCV core-mediated synergism of JNK activation was also detected in stable cells expressing HCV core protein. Furthermore, we demonstrate that HCV core protein does not compete with TNF receptor-associated death domain (TRADD) for its interaction with the death domain of TNFR1. Our in vivo data show that HCV core and TRADD form a ternary complex with TNFR1. These findings suggest that the HCV core protein modulates TNFR1 signaling and may, thus, play a role in chronic infection of HCV patients.

Apoptosis↗

Surface measurements of global warming causing atmospheric constituents in Korea.

The expansion of the industrial economy and the increase of population in Northeast Asian countries have caused much interest in climate monitoring related to global warming. However, new techniques and better platforms for the measurement of global warming and regional databases are still old-fashioned and are not being developed sufficiently. With respect to this agenda, since 1993, at the request of the World Meteorological Organization (WMO), to monitor functions of global warming, the Korea Meteorological Administration (KMA) has set up a Global Atmospheric Watch (GAW) Station on the western coast of Korea (Anmyun-do) and has been actively monitoring global warming over Northeast Asia. In addition, atmospheric carbon dioxide (CO2) has been measured for a similar KMA global warming program at Kosan, Cheju Island since 1990. Aerosol and radiation have also been measured at both sites as well as in Seoul. The observations have been analyzed using diagnostics of climate change in Northeast Asia and also have been internationally compared. Results indicate that greenhouse gases are in good statistic agreement with the NOAA/Climate Monitoring and Diagnostics Laboratory (CMDL) long-term trends of monthly mean concentrations and seasonal cycles. Atmospheric particulate matter has also been analyzed for particular Asian types in terms of optical depth, number concentration and size distribution.

Aerosols↗

Flight kinematics of the barn swallow (Hirundo rustica) over a wide range of speeds in a wind tunnel.

Two barn swallows (Hirundo rustica) flying in the Lund wind tunnel were filmed using synchronised high-speed cameras to obtain posterior, ventral and lateral views of the birds in horizontal flapping flight. We investigated wingbeat kinematics, body tilt angle, tail spread and angle of attack at speeds of 4-14 ms(-1). Wingbeat frequency showed a clear U-shaped relationship with air speed with minima at 8.9 ms(-1)(bird 1) and 8.7 ms(-1) (bird 2). A method previously used by other authors of estimating the body drag coefficient (C(D,par)) by obtaining agreement between the calculated minimum power (V(min)) and the observed minimum wingbeat frequency does not appear to be valid in this species, possibly due to upstroke pauses that occur at intermediate and high speeds, causing the apparent wingbeat frequency to be lower. These upstroke pauses represent flap-gliding, which is possibly a way of adjusting the force generated to the requirements at medium and high speeds, similar to the flap-bound mode of flight in other species. Body tilt angle, tail spread and angle of attack all increase with decreasing speed, thereby providing an additional lift surface and suggesting an important aerodynamic function for the tail at low speeds in forward flight. Results from this study indicate the high plasticity in the wingbeat kinematics and use of the tail that birds have available to them in order to adjust the lift and power output required for flight.

Animals↗

A single point mutation in HIV-1 V3 loop alters the immunogenic properties of rgp120.

The results of the study presented in this report show that clones of env derived from genetically divergent HIV-1 field isolates fall into two major subsets based on the predicted secondary structure of the V3 region in gp120. One subset exemplified by the clones A-UG06c, B-RT3.12 and C-UG045 is predicted to assume a beta-turn conformation in the V3 loop and comprises the GPGX residues. The other subset exemplified by the clones D-UG23c and D-UG042 (GXGX) are deficient in the expression of the beta-turn in the loop. Since secondary conformations are highly likely to confer antigenic properties in a protein backbone at least for B cells, we have used nucleic acid immunization to test the effect of the beta-turn deficiency on the immunogenic potential of rgp120 encoded in these field isolates. As hypothesized, inoculation of BALB/c mice with the env plasmid encoding the beta-turn expressing rgp120 molecules resulted in the development of a vigorous antibody response to the homologous V3 loop peptides. In contrast, immunization with an rgp120 clone deficient in the beta-turn in the V3 loop showed no evidence of antibody development to the V3 loop. Instead, the latter clones triggered T cell proliferative responses and markedly increased the level of IL-2 and IFN-gamma production by T cells. Significantly, reconstitution of the beta-turn conformation by site-directed mutagenesis of a single V3 loop residue yielded rgp120 molecules which restored antibody production while diminishing the cell-mediated immune (CMI) responses to the V3 residue. These observations demonstrate the marked impact of a single amino acid substitution on the immunogenic properties of V3 region in gp120 encoded by divergent HIV-1 field isolates.

Amino Acid Sequence↗

Dehydroepiandrosterone and melatonin prevent Bacillus anthracis lethal toxin-induced TNF production in macrophages.

The lethal toxin of Bacillus anthracis, which is composed of two separate proteinaceous exotoxins, namely protective antigen and lethal factor, is central to the pathogenesis of anthrax. Low levels of this toxin are known to induce release of cytokines such as tumor necrosis factor alpha (TNF-alpha). In the present study we investigated the effect of dehydroepiandrosterone (DHEA), melatonin (MLT), or DHEA + MLT on production of lethal toxin-induced TNF-alpha in mouse peritoneal macrophages. We found that treatment with DHEA significantly inhibited the TNF-alpha production caused by anthrax lethal toxin. Exposure of MLT to anthrax lethal toxin-treated macrophages also decreased the release of TNF-alpha to the extracellular medium as compared to the control. However, combined use of DHEA and MLT also inhibited TNF-alpha release, but not more than single therapies. These results suggest that DHEA and MLT may have a therapeutic role in reducing the increased cytokine production induced by anthrax lethal toxin.

Adjuvants, Immunologic↗

Intracellular calcium antagonist protects cultured peritoneal macrophages against anthrax lethal toxin-induced cytotoxicity.

The lethal toxin of Bacillus anthracis is central to the pathogenesis of anthrax. Using primary cultures of mouse peritoneal macrophages, we have demonstrated that intracellular calcium release inhibitors protect against anthrax lethal toxin-induced cytotoxicity. The cytolytic effect of anthrax lethal toxin was markedly reduced by dantrolene, an inhibitor of calcium release from intracellular calcium stores. Pretreatment of macrophages with cyclosporin A, which has been shown to be a potent inhibitor of calcium release from mitochondria, also protected cells against cytotoxicity. These results indicate that calcium release from intracellular store may be an essential step for the propagation of anthrax lethal toxin-induced cell damage in macrophages. Thus our findings suggest that dantrolene, cyclosporin A, and possibly other drugs affecting intracellular calcium pools might be effectively preventing the toxicity from anthrax lethal toxin.

Animals↗

Hypersensitivity pneumonitis caused by Fusarium napiforme in a home environment.

BACKGROUND: We report a case of hypersensitivity pneumonitis (HP) in a 17-year-old male student caused by Fusarium napiforme found in his home environment. METHODS: The patient was diagnosed according to history, chest radiograph, spirometry, high-resolution chest CT, and transbronchial lung biopsy. To identify the causative agent, cultured aeromolds were collected by the open-plate method. From the main fungi cultured, fungal antigens were prepared, and immunoblot analysis with the patient's serum and each fungal antigen was performed. RESULTS: Five fungal species were isolated from the patient's home. Immunoblotting analysis with the patient's serum demonstrated more than 10 IgG-binding fractions to F. napiforme extract only, while little binding was noted with the other fungal antigens. CONCLUSIONS: We should be aware that HP may be caused by F. napiforme in the home environment.

Adolescent↗

Carotid artery stenting in patients with symptomatic coronary artery disease.

Carotid artery stenting has been accepted as a potential alternative to carotid endarterectomy in patients with significant carotid artery stenosis. The objective of this study was to evaluate the feasibility, safety and long-term outcome of percutaneous stenting of carotid artery stenosis in patients with coexisting symptomatic coronary disease. Between May 1996 and May 1999, we performed carotid artery stenting at 48 lesions in 36 patients with carotid stenosis of 60% and symptomatic coronary artery stenosis. Twenty-one patients (58%) had neurologic symptoms. Carotid stenting was performed in 43 internal, 2 external and 3 common carotid lesions. We used Wallstent in 46 lesions, Palmaz stent in 2 lesions and Microstent II in 1 lesion. Staged or combined coronary intervention was performed in 18 patients (50%) and staged coronary artery bypass surgery was performed in 6 patients (17%). In the other 12 patients (33%), medical treatments were performed. Carotid stenting was successful in all lesions. Simultaneous bilateral carotid stenting was performed in 11 patients (31%). One major and 1 minor stroke developed during the procedure. There were no deaths during the procedures and within 30 days post-procedure. During the follow-up of 14 +/- 7 (3 to 40) months, there were no deaths or neurological events. On follow-up (6 +/- 1 months) angiography and/or duplex sonography of 44 eligible lesions in 32 patients, there were 2 cases of asymptomatic restenosis (4.5%) which developed in Palmaz stents implanted at the external carotid artery and the common carotid artery, respectively. In conclusion, carotid artery stenting in patients with coexistent carotid and coronary artery disease is feasible, safe and shows favorable follow-up outcomes.

Aged↗

Cell cycle arrest mediated by hepatitis delta antigen.

Hepatitis delta antigen (HDAg) is the only viral-encoded protein of the hepatitis delta virus (HDV). This protein has been extensively characterized with respect to its biochemical and functional properties. However, the molecular mechanism responsible for persistent HDV infection is not yet clear. Previously, we reported that overexpression of HDAg protects insect cells from baculovirus-induced cytolysis [Hwang, S.B. Park, K.-J. and Kim, Y.S. (1998) Biochem. Biophys. Res. Commun. 244, 652-658]. Here we report that HDAg mediates cell cycle arrest when overexpressed in recombinant baculovirus-infected insect cells. Flow cytometry analysis has shown that HDAg expression in Spodoptera frugiperda cells causes an accumulation of substantial amounts of polyploid DNA in the absence of cell division. This phenomenon may be partly responsible for the persistent infection of chronic HDV patients.

Animals↗

A novel parvovirus isolated from Manchurian chipmunks.

A novel parvovirus was identified in Manchurian chipmunks inhabiting Korea. Hepatitis B surface antigen (HBsAg) was detected in sera from 4 animals among 62 apparently healthy chipmunks. Electron microscopic examination of the HBsAg-positive sera revealed virus-like spherical particles 20-22 nm in diameter. Extraction of nucleic acid under annealing conditions from the serum samples containing virus-like particles yielded a single species of DNA molecule with the electrophoretic mobility of 5.6-kb double-stranded DNA. Four overlapping clones that encompassed almost the full-length viral genome, except both ends, were obtained. By sequencing these clones, we determined the sequence of 5097 nucleotides of the viral DNA. Two open reading frames were identified, with the left side open reading frame encoding a putative nonstructural protein and the right side open reading frame encoding a putative capsid protein. The nucleotide and amino acid sequences showed significant homology to parvovirus B19 and simian parvovirus, but showed little homology to other mammalian autonomous parvoviruses or adeno-associated viruses. These observations indicate that the virus isolated from Manchurian chipmunks is a novel parvovirus and may be a potentially useful animal model of human B19 infection as a new member of the Erythrovirus genus of the Parvoviridae.

Amino Acid Sequence↗

Suspected hereditary nonpolyposis colorectal cancer: International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) criteria and results of genetic diagnosis.

PURPOSE: The aim of this study was to determine the frequency of mutations in the mismatch repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. METHODS: We devised two criteria for families suspected of having hereditary nonpolyposis colorectal cancer (Criteria I and II). Criteria I consist of at least two first-degree relatives affected with colorectal cancer with at least one of the following: development of multiple colorectal tumors including adenomatous polyp, at least one colorectal cancer case diagnosed before the age of 50, and occurrence of a hereditary nonpolyposis colorectal cancer extracolonic cancer (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, or ovary) in family members. Criteria II consist of one colorectal cancer patient with at least one of the following: early age of onset (<40 years); endometrial, urinary tract, or small intestine cancer in the index patient or a sibling (one aged <50 years); and two siblings with other integral hereditary nonpolyposis colorectal cancer extracolonic cancers (one aged <50 years). A questionnaire was mailed to members of the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer to determine the mutation detection rate in mismatch repair genes from the families fulfilling these criteria. For comparison the mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria in each institution was also obtained. RESULTS: Data were obtained from eight different institutions (in 7 different countries). In a total of 123 patients from 123 families (67 families fulfilling Criteria I and 56 families fulfilling Criteria II), genetic testing for germline mismatch repair gene variants was performed. Germline mutations of the hMLH1 or hMSH2 genes were identified in 24 families (20 percent). Of these, the mutation detection rate for families fulfilling Criteria I was 28 percent (19/67). The mutation detection rate for families fulfilling Criteria II was 9 percent (5/56). In these eight institutions, the overall mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria was 50 percent (77/154). CONCLUSION: The Criteria I for suspected hereditary nonpolyposis colorectal cancer have the advantages that they can be applied to nuclear families and they can include extracolonic cancers. The results of this study suggest that families fulfilling Criteria I should be offered genetic testing. The relatively low mutation detection rate in those families fulfilling Criteria II suggests that, using current techniques, genetic testing in these families is not practical.

Age of Onset↗