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1.  Identification and characterization of seed-specific transcription factors regulating anthocyanin biosynthesis in black rice 
Journal of Applied Genetics  2011;52(2):161-169.
Black rice is rich in anthocyanin and is expected to have more healthful dietary potential than white rice. We assessed expression of anthocyanin in black rice cultivars using a newly designed 135 K Oryza sativa microarray. A total of 12,673 genes exhibited greater than 2.0-fold up- or down-regulation in comparisons between three rice cultivars and three seed developmental stages. The 137 transcription factor genes found to be associated with production of anthocyanin pigment were classified into 10 groups. In addition, 17 unknown and hypothetical genes were identified from comparisons between the rice cultivars. Finally, 15 out of the 17 candidate genes were verified by RT-PCR analysis. Among the genes, nine were up-regulated and six exhibited down-regulation. These genes likely play either a regulatory role in anthocyanin biosynthesis or are related to anthocyanin metabolism during flavonoid biosynthesis. While these genes require further validation, the results here underline the potential use of the new microarray and provide valuable insight into anthocyanin pigment production in rice.
doi:10.1007/s13353-011-0027-3
PMCID: PMC3088801  PMID: 21286901
Anthocyanin; Black rice; Pigmentation; Rice microarray; Transcription factor
2.  Anti-oxidative neuroprotection by estrogens in mouse cortical cultures. 
Journal of Korean Medical Science  2000;15(3):327-336.
Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.
PMCID: PMC3054631  PMID: 10895977
3.  Utilisation of combined 18F-FDG PET/CT scan for differential diagnosis between benign and malignant adrenal enlargement 
The British Journal of Radiology  2013;86(1028):20130190.
Objective:
To assess the properties of adrenal lesions with and without known primary cancer and investigate predictors for differential diagnosis between benign and malignant adrenal enlargement.
Methods:
This retrospective study used fluorine-18 fludeoxyglucose positron emission tomography (PET)/CT in 325 patients with adrenal lesions (229 with known primary cancer and 96 without primary cancer). Age, sex, the presence of right and left masses, nodules or hyperplasia, unenhanced attenuation, maximum standardised uptake value (SUVmax) ratio, and the presence of metastasis in other body parts and locations of the primary cancer were assessed. Univariate and multivariate analyses were used to assess variables associated with risk of adrenal metastasis.
Results:
Patients with adrenal metastasis vs those without had a higher frequency of primary lung cancer (52.3% vs 30.7%) but a lower frequency of gastrointestinal cancer (7.9% vs 16.6%). The frequency of other abnormalities, including adenoma and hyperplasia, was similar between patients with and without known primary cancer. A higher proportion of patients with adrenal metastasis regardless of primary cancer site were younger, had a nodule or a mass, had an unenhanced attenuation of >10 HU, had an SUVmax ratio of >2.5, and had metastasis in other body parts. Analysis found independent associations of age, unenhanced attenuation of >10 HU, SUVmax ratio of >2.5 and the presence of metastasis in other body parts with adrenal metastasis. The combination of the four variables was strongly associated with adrenal metastasis.
Conclusion:
PET/CT was useful in characterising adrenal lesions as benign or malignant and helpful in identifying adrenal metastasis and cancer severity.
Advances in knowledge:
PET/CT can help in the differential diagnosis between benign and malignant adrenal enlargement.
doi:10.1259/bjr.20130190
PMCID: PMC3745059  PMID: 23833032
4.  Effect of public deliberation on attitudes toward surrogate consent for dementia research 
Neurology  2011;77(24):2097-2104.
Objective:
To assess the informed, deliberative views of the older general public toward a policy of allowing surrogate consent for Alzheimer disease (AD) research.
Methods:
A total of 503 persons aged 50+ recruited by random digit dialing were randomly assigned to 1 of 3 groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after deliberation session (or equivalent time), and 1 month after the session, regarding their attitudes toward a policy of allowing surrogate consent for research studies of varying risks and potential benefits (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial).
Results:
At baseline, a policy of surrogate consent for AD research was supported by 55%–91%, depending on the scenario. The education group had a transient increase in support for one research scenario after receiving the information materials. In the deliberation group, support for surrogate consent was higher after deliberation for all scenarios (67% to 97%), with much of the increase sustained 1 month after the deliberation session. No changes occurred in the control group. The study's limitations include self-selection of participants due to the demanding nature of attendance at the deliberation sessions.
Conclusions:
This sample of the older general public generally supported a policy of surrogate consent for AD research at baseline. Their support increased with democratic deliberation involving informed, in-depth exploration of the relevant scientific and ethical issues.
doi:10.1212/WNL.0b013e31823648cb
PMCID: PMC3235352  PMID: 21975207
5.  Wound-Healing Potential of Cultured Epidermal Sheets Is Unaltered after Lyophilization: A Preclinical Study in Comparison to Cryopreserved CES 
BioMed Research International  2013;2013:907209.
Lyophilized Cultured Epidermal Sheets (L-CES) have been reported to be as effective as the cryopreserved CES (F-CES) in treating skin ulcers. However, unlike F-CES, no preclinical study assessing wound-healing effects has been conducted for L-CES. The present study was set out to investigate the microstructure, cytokine profile, and wound-healing effects of L-CES in comparison to those of F-CES. Keratinocytes were cultured to prepare CES, followed by cryopreservation at −70°C and lyophilization. Under microscopic observation, intact cells with apparent intracellular junctions were observed in L-CES. The L-CES, like fresh CES, consisted of three to four well-maintained epidermal layers, as shown by the expression of keratins, involucrin, and p63. There were no differences in the epidermal layer or protein expression between L-CES and F-CES, and both CES were comparable to fresh CES. TGF-α, EGF, VEGF, IL-1α, and MMPs were detected in L-CES at levels similar to those in F-CES. In a mouse study, wounds treated with L-CES or F-CES completely healed at least 4 days faster than untreated wounds. CES-treated wounds completely healed by day 10, while the untreated wounds did not heal by day 14. Masson's trichrome staining showed that collagen deposition in the CES-treated wounds was highly increased in the dermis of the wound center compared to that in the control wounds. Thus, this study demonstrates that L-CES is as clinically effective as F-CES for wound treatment.
doi:10.1155/2013/907209
PMCID: PMC3878849  PMID: 24455737
6.  International models of investigator-initiated trials: implications for Japan 
Annals of Oncology  2012;23(12):3151-3155.
Background
Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials.
Materials
In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world.
Results
In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval.
Conclusions
To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.
doi:10.1093/annonc/mds168
PMCID: PMC3501232  PMID: 22843420
academic/institutional investigator-initiated clinical trials; anticancer drugs; good clinical practice; health care policy; international clinical trials; patient advocates
7.  Surrogate consent for dementia research 
Neurology  2009;72(2):149-155.
Background
Research in novel therapies for Alzheimer disease (AD) relies on persons with AD as research subjects. Because AD impairs decisional capacity, informed consent often must come from surrogates, usually close family members. But policies for surrogate consent for research remain unsettled after decades of debate.
Methods
We designed a survey module for a random subsample (n = 1,515) of the 2006 wave of the Health and Retirement Study, a biennial survey of a nationally representative sample of Americans aged 51 and older. The participants answered questions regarding one of four randomly assigned surrogate-based research (SBR) scenarios: lumbar puncture study, drug randomized control study, vaccine study, and gene transfer study. Each participant answered three questions: whether our society should allow family surrogate consent, whether one would want to participate in the research, and whether one would allow one’s surrogate some or complete leeway to override stated personal preferences.
Results
Most respondents stated that our society should allow family surrogate consent for SBR (67.5% to 82.5%, depending on the scenario) and would themselves want to participate in SBR (57.4% to 79.7%). Most would also grant some or complete leeway to their surrogates (54.8% to 66.8%), but this was true mainly of those willing to participate. There was a trend toward lower willingness to participate in SBR among those from ethnic or racial minority groups.
Conclusions
Family surrogate consent–based dementia research is broadly supported by older Americans. Willingness to allow leeway to future surrogates needs to be studied further for its ethical significance for surrogate-based research policy.
doi:10.1212/01.wnl.0000339039.18931.a2
PMCID: PMC2663398  PMID: 19139366
8.  Surrogate consent for dementia research 
Neurology  2009;72(2):149-155.
Background:
Research in novel therapies for Alzheimer disease (AD) relies on persons with AD as research subjects. Because AD impairs decisional capacity, informed consent often must come from surrogates, usually close family members. But policies for surrogate consent for research remain unsettled after decades of debate.
Methods:
We designed a survey module for a random subsample (n = 1,515) of the 2006 wave of the Health and Retirement Study, a biennial survey of a nationally representative sample of Americans aged 51 and older. The participants answered questions regarding one of four randomly assigned surrogate-based research (SBR) scenarios: lumbar puncture study, drug randomized control study, vaccine study, and gene transfer study. Each participant answered three questions: whether our society should allow family surrogate consent, whether one would want to participate in the research, and whether one would allow one’s surrogate some or complete leeway to override stated personal preferences.
Results:
Most respondents stated that our society should allow family surrogate consent for SBR (67.5% to 82.5%, depending on the scenario) and would themselves want to participate in SBR (57.4% to 79.7%). Most would also grant some or complete leeway to their surrogates (54.8% to 66.8%), but this was true mainly of those willing to participate. There was a trend toward lower willingness to participate in SBR among those from ethnic or racial minority groups.
Conclusions:
Family surrogate consent–based dementia research is broadly supported by older Americans. Willingness to allow leeway to future surrogates needs to be studied further for its ethical significance for surrogate-based research policy.
GLOSSARY
= Alzheimer disease;
= confidence interval;
= Health and Retirement Study;
= legally authorized representatives;
= lumbar puncture;
= odds ratio;
= randomized controlled trial;
= surrogate-based research.
doi:10.1212/01.wnl.0000339039.18931.a2
PMCID: PMC2663398  PMID: 19139366
9.  Uterine cavernous haemangioma in a post-menopausal woman: CT and MRI findings mimicking uterine myoma with degeneration 
The British Journal of Radiology  2011;84(1000):e68-e71.
Cavernous haemangioma is a very rare vascular malformation of the uterus. We describe the CT and MRI findings of a cavernous haemangioma in an 81-year-old female with recurrent menorrhagia. CT showed a well-marginated mass with multifocal calcifications and extensive haemorrhage, as well as necrosis in the anterior wall of the uterus. MRI revealed heterogeneous low- to high-signal intensities of the mass on T1 and T2 weighted images as well as portions with poor enhancement of the mass on contrast-enhanced T1 weighted images. Although rare, cavernous haemangioma should be included in the differential diagnosis of a calcified haemorrhagic necrotic uterine mass in post-menopausal women.
doi:10.1259/bjr/56484373
PMCID: PMC3473473  PMID: 21415295
10.  Differences in radiological/HRCT findings in eosinophilic bronchitis and asthma: implication for bronchial responsiveness 
Thorax  2005;61(1):41-47.
Background
Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics.
Methods
Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography.
Results
WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, p = 0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls.
Conclusion
WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.
doi:10.1136/thx.2005.044420
PMCID: PMC2080709  PMID: 16244090
asthma; eosinophilic bronchitis; high resolution computed tomography; airway hyperresponsiveness
11.  A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κB promotes gastric tumour growth and angiogenesis 
British Journal of Cancer  2010;104(1):166-174.
Background:
The underlying mechanisms involved in the activation of hypoxia-inducible factor-1 (HIF-1) in gastric cancer remain unclear. As nuclear factor-κB (NF-κB) as well as HIF-1 have been implicated in angiogenesis of various cancers, we investigated their relationship in gastric cancer.
Methods:
Nuclear expressions of HIF-1α and NF-κB/RelA were assessed in 251 human gastric carcinoma specimens by immunohistochemical tissue array analysis. Stable human gastric cancer cells, infected with a retroviral vector containing super-suppressive mutant form of IκBα (IκBαM), were used for animal studies as well as cell culture experiments. Xenografted tumours were measured and IκBαM effects on angiogenesis and HIF-1α activation were assessed by immunohistochemistry, western blotting, luciferase reporter assay, and semiquantitative reverse transcription–polymerase chain reaction. In addition, NF-κB effects on the HIF-1α degradation and synthesis were examined.
Results:
Hypoxia-inducible factor-1α activation positively correlated with RelA activation in clinical gastric cancer samples (P<0.001). The IκBαM overexpression suppressed tumour growth, microvessel density, and HIF-1α activation in xenografted tumours. Cell culture experiments showed that hypoxia-induced HIF-1α expression was reduced by NF-κB inhibition under hypoxic conditions at the translational level.
Conclusion:
The hypoxia-dependent activation of the NF-κB/HIF-1α/VEGF pathway contributes, at least in part, to gastric cancer promotion via enhancement of angiogenesis.
doi:10.1038/sj.bjc.6606020
PMCID: PMC3039796  PMID: 21119667
HIF-1α; NF-κB; gastric cancer; tumour growth; angiogenesis; hypoxia
12.  Association of MCP-1 and CCR2 polymorphisms with the risk of late acute rejection after renal transplantation in Korean patients 
Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125–6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.
doi:10.1111/j.1744-313X.2007.00725.x
PMCID: PMC2228509  PMID: 18186797
13.  Congenital angiomyoma of the tongue: case report 
Dentomaxillofacial Radiology  2010;39(7):446-448.
Angiomyomas of the oral cavity are rare benign vascular neoplasms. In particular, the congenital form has not been reported before in the English language literature. We present a congenital angiomyoma of the tongue that was found on the posterior middle of the tongue in an infant. On MRI, the mass showed an isointense signal to muscle on the T1 weighted image and a slightly hyperintense signal on the T2 weighted image. Immunohistochemically, tumour cells were positive to desmin and smooth muscle actin, but negative to vimentin and S100. The treatment was surgical excision and no recurrence was found during the 26 month follow-up period.
doi:10.1259/dmfr/32524441
PMCID: PMC3520187  PMID: 20841464
angiomyoma; tongue neoplasm; magnetic resonance imaging
14.  Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study 
Purpose:
We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.
Materials and methods:
The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of ≥ 8 voids per 24 h and episodes of urgency or urgency incontinence ≥ 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King’s Health Questionnaire.
Results:
A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).
Conclusions:
Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.
doi:10.1111/j.1742-1241.2008.01898.x
PMCID: PMC2680337  PMID: 19143854
15.  A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer 
British Journal of Cancer  2007;96(10):1514-1519.
Capecitabine, a prodrug of 5-FU, has been reported to generate maximal tumour activity at tumour sites and/or to improve drug tolerability as compared with 5-FU infusion, and it has also been demonstrated to act synergistically with irinotecan against some solid cancers. A previous study concluded that dose-intensified biweekly capecitabine seems to be more effective at increasing both response rate and progression-free survival time than conventional dose and schedule of capecitabine in colon cancer. We conducted this study to ascertain the efficacy and toxicity of dose-intensified biweekly capecitabine and irinotecan combination chemotherapy in chemotherapy-naïve advanced or metastatic gastric cancer patients. Patients were treated with irinotecan 130 mg m−2 intravenously for 90 min on days 1 and 15. Capecitabine at 3500 mg m−2 day−1, divided into two sessions per day, was administered for seven consecutive days from days 1 and 15, and followed by a 7-day drug-free period, respectively. Fifty-five eligible patients were enrolled in this study from November 2003 to April 2006. There were 22 women and 33 men: median patient age was 54 years (range: 27–81). A total of 200 treatment cycles were administered at a median number of four per patient (range: 1–9). Intent-to-treatment analysis showed that one patient achieved complete response (1.8%), 23 partial response (41.8%), 15 stable disease (27.3%), 10 progressive disease (18.2%) and 6 were non-evaluable (10.9%). The overall response rate was 43.6% (95% confidence interval: 30.2–56.9). The common grade 3–4 toxicities were neutropenia in 12 (21.8%), nausea/vomiting in 3 (5.4%) and diarrhea in 4 (7.2%) patients. Median time to progression was 5 months (range: 0.5–11 months), median survival duration was 11 months (range: 0.5–45 months) and median response duration was 6 months (range: 0.5–9 months). Biweekly dose-intensified capecitabine and irinotecan combination chemotherapy was active for the treatment of advanced or metastatic gastric cancers with a tolerable safety profile.
doi:10.1038/sj.bjc.6603752
PMCID: PMC2359951  PMID: 17473829
irinotecan; capecitabine; stomach neoplasms
16.  Surgical and pathological outcomes of laparoscopic surgery for transverse colon cancer 
Purpose
Several multi-institutional prospective randomized trials have demonstrated short-term benefits using laparoscopy. Now the laparoscopic approach is accepted as an alternative to open surgery for colon cancer. However, in prior trials, the transverse colon was excluded. Therefore, it has not been determined whether laparoscopy can be used in the setting of transverse colon cancer. This study evaluated the peri-operative clinical outcomes and oncological quality by pathologic outcomes of laparoscopic surgery for transverse colon cancer.
Materials and methods
Analysis of the medical records of patients who underwent laparoscopic colorectal resection from August 2004 to November 2007 was made. Computed tomography, barium enema, and colonoscopy were performed to localize the tumor preoperatively. Extended right hemicolectomy, transverse colectomy, and extended left hemicolectomy were performed for transverse colon cancer. Surgical outcomes and pathologic outcomes were compared between transverse colon cancer (TCC) and other site colon cancer (OSCC).
Results
Of the 312 colorectal cancer patients, 94 patients underwent laparoscopic surgery for OSCC, and 34 patients underwent laparoscopic surgery for TCC. Patients with TCC were similar to patients with OSCC in age, gender, body mass index, operating time, blood loss, time to pass flatus, start of diet, hospital stay, tumor size, distal resection margin, proximal resection margin, number of lymph nodes, and radial margin. One case in TCC and three cases in OSCC were converted to open surgery.
Conclusions
Laparoscopic surgery for transverse colon cancer and OSCC had similar peri-operative clinical and acceptable pathological outcomes.
doi:10.1007/s00384-008-0471-7
PMCID: PMC2386750  PMID: 18379794
Laparoscopy; Transverse colon; Colon cancer
17.  Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer 
British Journal of Cancer  2005;92(5):827-831.
We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m−2 intravenously (i.v.) for 1 h and then cisplatin 75 mg m−2 i.v. for 2 h on day 1. Oral UFT at 400–600 mg day−1, as determined by body surface area, and leucovorin at 75 mg day−1 were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4–63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6–152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.
doi:10.1038/sj.bjc.6602446
PMCID: PMC2361894  PMID: 15726097
docetaxel; cisplatin; UFT; stomach neoplasms
18.  Clinical characteristics of constrictive pericarditis diagnosed by echo-Doppler technique in Korea. 
Journal of Korean Medical Science  2001;16(5):558-566.
A retrospective analysis of clinical data of 71 patients with constrictive pericarditis (CP) diagnosed by echo-Doppler technique (mean age, 49+/-17) was done. In 27 patients (38%), the etiology was unknown, and the three most frequent identifiable causes were tuberculosis (23/71, 32%), cardiac surgery (8/71, 11%), and mediastinal irradiation (6/71, 9%). Pericardiectomy was performed in 35 patients (49%) with a surgical mortality of 6% (2/35), and 11 patients (15%, 11/ 71) showed complete resolution of constrictive physiology with medical treatment. Patients with transient CP were characterized by absence of pericardial calcification, shorter symptom duration, and higher incidence of fever, weight loss, and tuberculosis. The 5-yr survival rates of patients with transient CP and those undergoing pericardiectomy were 100% and 85+/-6%, respectively, which were significantly higher than that of patients without undergoing pericardiectomy (33+/-17%, p=0.0083). Mediastinal irradiation, higher functional class, low voltage in ECG, low serum albumin, and old age were the independent variables associated with a higher mortality. Tuberculosis is still the most important etiology of CP in Korea, and not infrequently, it may cause transient CP. Early diagnosis and decision-making using follow-up echocardiography are crucial to improve the prognosis of patients with CP.
PMCID: PMC3057598  PMID: 11641523
19.  Altered remodeling of nucleolar machineries in cultured hepatocytes treated with thioacetamide. 
Thioacetamide (TA) is converted into a hyperacetylating agent which causes hepatic necrosis, regeneration, cirrhosis and cancerous transformation. One of the most characteristic toxicities of TA in rat is observed with a 50 mg/kg per day which induces nucleolar enlargement different from that in regenerating liver. From TA-treated liver, the nucleoli were isolated and characterized for an altered nucleolar signal transduction system. Immunochemistry revealed that the poisoned nucleoli had increased levels of both nucleolus specific proteins (nucleophosmin and nucleolin) and various signal molecules (CK2, Erk1/2, p38, protein kinases A and C, and cyclin A). Using flow cytometry, the nucleoli were found to be in G2-arrested nuclei. Manifestation of the nucleolar enlargement could be readily observed using an ex vivo hepatocyte culture. There were two types of nucleolar enlargement. One was observed in normal hepatocytes with light density of enlarged nucleoli. The other was in TA-treated hepatocytes with dense and compact density of enlarged nucleoli, which contained a 3 to 5-fold higher nudeophosmin content than the control. In vitro induction of nucleolar enlargement with TA was possible. As soon as the hepatocytes anchored on a collagen coat, exogeneous TA (higher than 1 microg/mL) could induce dense and compact nucleoli. However, when an exogeneous drug was added after monolayer formation (1 day), no drug-induced nucleolar enlargement was observed.
PMCID: PMC3054557  PMID: 11289405
20.  Tetraparesis associated with ossification of the posterior longitudinal ligament of the cervical spine 
International Orthopaedics  1999;23(4):247-248.
Abstract 
This is a case report of tetraparesis associated with extraordinarily severe ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. There was no history of trauma. The object of this paper is to show that OPLL can progress relentlessly to a nearly complete quadriplegia even without trauma, but that adequate decompression can produce almost complete recovery.
doi:10.1007/s002640050362
PMCID: PMC3619751  PMID: 10591946
21.  Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison with intracoronary Doppler method. 
Journal of Korean Medical Science  2000;15(2):139-145.
To evaluate the feasibility and usefulness of transthoracic Doppler echocardiography (TTDE) as a non-invasive method in recording distal anterior descending (LAD) coronary flow velocity, we compared coronary flow reserve (CFR) measured by TTDE with measurements by intracoronary Doppler wire (ICDW). Twenty-one patients without LAD stenosis were studied. ICDW performed at baseline and after intracoronary injection of 18 microg adenosine. TTDE was performed at baseline and after intravenous adenosine (140 microg/kgmin for 2 min). Adequate Doppler recordings of coronary flow velocities during systole were obtained in 14 of 21 study patients (67%) and during diastole in 17 (81%) patients. Baseline and hyperemic peak diastolic flow velocities measured by TTDE were significantly smaller than those obtained by ICDW (p<0.05). However, diminishing trends of diastolic and systolic velocity ratio after hyperemia were similarly observed in both methods. CFR obtained by TTDE (3.0+/-0.5), was higher than the value calculated by ICDW (2.5+/-0.4). There were significant correlations between the values obtained by the two methods (r=0.72, p<0.01). It is concluded that TTDE is a feasible method in measuring coronary flow velocity and appears to be a promising non-invasive method in evaluating CFR.
PMCID: PMC3054624  PMID: 10803688
22.  Treatment of ventricular tachycardia-induced cardiomyopathy by transcatheter radiofrequency ablation. 
Heart  1996;76(6):550-552.
Catheter ablation of ventricular tachycardia was successfully performed in a patient with dilated cardiomyopathy (ejection fraction 38%) and a long history of repetitive palpitations. Holter monitoring showed ventricular tachycardia that had a left bundle branch block QRS configuration with inferior axis deviation and was present for about one third of the daytime hours. At electrophysiological testing, ventricular tachycardia was reproduced by isoprenaline infusion. Radiofrequency energy delivered to the right ventricular outflow tract was successful at preventing the induction of ventricular tachycardia. Left ventricular ejection fraction had improved from 38% to 48% one month after ablation. During the follow up period of one year the patient remained free from arrhythmia on no medication. The ejection fraction was 61% one year after ablation. This report confirms that dilated cardiomyopathy can be induced by ventricular tachycardia and demonstrates that dilated cardiomyopathy can be reversed if the tachycardia is abolished by radiofrequency catheter ablation.
PMCID: PMC484612  PMID: 9014808
23.  Treatment of intertrochanteric fracture with the Gamma AP locking nail or by a compression hip screw – a randomised prospective trial 
International Orthopaedics  1998;22(3):157-160.
Abstract.
The Gamma AP (Asia-Pacific) locking nail (GAPN) is a modification of the standard Gamma locking nail made especially for use in Oriental patients. We made a randomised prospective comparison of the compression hip screw (CHS) and the Gamma AP locking nail for the internal fixation of 60 intertrochanteric fractures of the hip in elderly patients by comparing perioperative details and analysing the radiographic and clinical results. The operation time for the GAPN group was shorter than for the CHS group and the intraoperative blood loss was lower. The Gamma AP nail enabled earlier mobilisation. We found no significant difference in the time to union and the length of sliding of the lag screw between the two groups. The decrease in the neck shaft angle in the Gamma nail group was significantly smaller than in the CHS patients. There were no significant mechanical complications, such as fracture of the femoral shaft or failure of fixation in the Gamma nail group. On the basis of our observations we conclude that the Gamma AP locking nail is more efficient than the CHS in the treatment of intertrochanteric fractures in geriatric patients.
doi:10.1007/s002640050231
PMCID: PMC3619600  PMID: 9728307
24.  Prophylaxis for deep vein thrombosis with aspirin or low molecular weight dextran in Korean patients undergoing total hip replacement;a randomized controlled trial 
International Orthopaedics  1998;22(1):6-10.
Summary.
150 Korean patients undergoing primary uncemented total hip replacement were randomized into 3 treatment groups for deep vein thrombosis (DVT) prophylaxis. Group A(50) were controls; Group B(50) received aspirin 1.2 g daily in 3 divided doses from 2 days before, to 14 days after surgery; Group C(50), received low molecular weight dextran 500 ml, infused intravenously at 50 ml/hour during surgery, and on each of the following 2 days. Contrast venograms were performed prior to surgery and 7 – 10 days after. The incidence of DVT was 20% in the control group, 12% in the aspirin group (p <0.1 vs control), and 6% in the dextran group (p <0.05 vs control). In patients developing DVT, the ratio of proximal to distal thrombi was increased in the control group as compared to treated groups (4 : 1 in the control group vs 1.5 : 1 in the treated groups). Both aspirin and dextran were well tolerated. Obesity (p <0.05) and long-term administration of steroids (p <0.05) were risk factors for deep vein thrombosis which reached statistical significance in the control group. Intraoperative venograms performed on 10 patients, showed that hip flexion (mean 40.4°) plus adduction (mean 11.5°) plus internal rotation (mean 81.5°), resulted in severe twisting or kinking of the femoral vein with stagnation of blood flow. Low molecular weight dextran significantly reduce the incidence of deep venous thrombosis and aspirin, though less effective, had a similar effect. Internal rotation of the hip joint should be minimized during operation in order to limit stagnation of blood flow in the femoral vein.
doi:10.1007/s002640050199
PMCID: PMC3619654  PMID: 9549575
25.  A prospective randomized study on the use of nadroparin calcium in the prophylaxis of thromboembolism in Korean patients undergoing elective total hip replacement 
International Orthopaedics  1998;21(6):399-402.
Summary.
Because of the belief that post-operative deep vein thrombosis (DVT) is rare in Asian patients, thromboprophylaxis is not usually prescribed for surgical patients. This study reports an open multi-centre controlled study of the use of a low molecular weight heparin, nadroparin calcium (Fraxoparine Sanofi France), as opposed to no prophylaxis in 100 patients undergoing uncemented total hip replacement. The patients had bilateral venography performed preoperatively and 10 days after operation. Eight patients (16%) developed DVT in the control group of 50 patients and 1 (2%) in the treatment group, also of 50 patients. Pulmonary embolus occurred in 1 patient in the treatment group and in 3 in the control group. Intraoperative and postoperative blood loss did not differ significantly between the two groups. Our study suggests that the incidence of DVT in Asian patients, though somewhat less than in their Western counterparts, is still considerable. It confirms the safety and efficacy of nadroparin calcium in preventing post-operative DVT in patients undergoing elective total hip replacement.
doi:10.1007/s002640050194
PMCID: PMC3619564  PMID: 9498151

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