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1.  Genetic susceptibility to COPD 
Thorax  2000;55(8):722.
doi:10.1136/thorax.55.8.722b
PMCID: PMC1745824  PMID: 10950722
2.  Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib 
British Journal of Cancer  2013;109(9):2309-2315.
Background:
This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib.
Methods:
Patients received oral dovitinib, 500 mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was evaluated by positron emission tomography (PET)–CT scans performed at baseline and after 4 weeks of treatment.
Results:
Between September 2011 and April 2012, 30 patients were enroled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient (3%) had a partial response. Based on the European Organization for Research and Treatment of Cancer PET response criteria, four patients (13%) had a metabolic partial response after 4 weeks of treatment. At a median follow-up of 8.3 months (range, 6.3–12.2 months), median progression-free survival (PFS) was 3.6 months (95% confidence interval (CI), 3.5–3.7 months) and median overall survival was 9.7 months (95% CI, 6.0–13.4 months). Metabolic progressive disease at Week 4 was significantly associated with shorter PFS (P=0.03). Grade 3/4 adverse events included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and hypertriglyceridaemia (10%). Most toxicities were manageable by dose modification.
Conclusion:
Dovitinib showed modest antitumour activity with manageable toxicities in heavily pretreated patients with advanced GISTs.
doi:10.1038/bjc.2013.594
PMCID: PMC3817332  PMID: 24084771
gastrointestinal stromal tumour; dovitinib; imatinib; sunitinib
3.  The Possibility of TBC1D21 as a Candidate Gene for Teat Numbers in Pigs 
Based on a quantitative traits locus (QTL) study using a F2 intercross between Landrace and Korean native pigs, a significant QTL affecting teat numbers in SSC7 was identified. The strong positional candidate gene, TBC1D21, was selected due to its biological function for epithelial mesenchymal cell development. Sequence analysis revealed six single nucleotide polymorphisms (SNPs) in the TBC1D21 gene. Among these, two SNP markers, one silent mutation (SNP01) for g.13,050A>G and one missense mutation (SNP04) for c.829A>T (S277C), were genotyped and they showed significant associations with teat number traits (p value = 6.38E-05 for SNP01 and p value = 1.06E-07 for SNP04 with total teat numbers). Further functional validation of these SNPs could give valuable information for understanding the teat number variation in pigs.
doi:10.5713/ajas.2013.13140
PMCID: PMC4093071  PMID: 25049720
QTL; SNP; SSC7; TBC1D21; Teat Number; Pig
4.  Growth of Ovarian Primary Follicles Retrieved from Neonates of Different Ages and Derivation of Mature Oocytes Following In vitro-Culture 
This study was conducted to improve the yield of mature oocytes from in vitro-culture of ovarian primary follicles by optimizing follicle retrieval from neonatal mice of different ages. Primary follicles of 75 to 99 μm in diameter were collected daily from 7- to 14-day-old neonatal mice, and subsequently cultured in α-MEM medium. Number of primary follicles isolated, growth of the follicle during in vitro-culture and maturation of intrafollicular oocytes were monitored. Overall, mean number of preantral follicles per animal was improved from 10.7 to 88.7 as the age of follicle donors was increased from 7 to 14-day-old. Number of primary follicles was increased gradually up to 11-day-old (35.7 follicle per an animal), then reduced to 29 in 14-day-old (p = 0.0013). More follicles retrieved from 10-day-old or 11-day-old females maintained their morphological normality at the end of primary culture than the follicles retrieved from 9-day-old. Of those cultured, primary follicles retrieved from 11-day-old mice yielded largest larger number of early secondary follicles than the follicles retrieved from in the other ages (39 vs. 13 to 29%). More than 3.3-times increase (0.86 to 2.86; p<0.05) in an average number of mature oocytes per animal was observed in the group of 11-day-old, compared with 9-day-old. However, no difference was found in the percentage of primary follicles developing into the pseudoantral stage (21 to 30%; p = 0.5222) and in the percentage of oocytes mucified (32 to 39%; p = 0.5792). In conclusion, a positive correlation between retrieval time and follicle growth was detected, which influences the efficiency to derive mature oocytes by follicle culture.
doi:10.5713/ajas.2010.10249
PMCID: PMC4093109  PMID: 25049606
Neonatal Mouse; Ovary; Primary Follicle; In vitro Culture; Oocyte Maturation
5.  A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer 
British Journal of Cancer  2009;101(10):1658-1663.
Background:
Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer.
Methods:
The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m−2; days 1 and 3), leucovorin (400 mg m−2; day 1), and 5-FU (2000 mg m−2; days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m−2; day 1), leucovorin (400 mg m−2; day 1), and 5-FU (2000 mg m−2; days 1 and 2) every 2 weeks.
Results:
Sixty-one patients were randomised to mFOLFIRI.3 (n=31) or mFOLFOX (n=30) regimen. The six-month survival rates were 27% (95% confidence interval (CI)=13–46%) and 30% (95% CI=15–49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI=10–42%) and 17% patients (95% CI=6–35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2).
Conclusion:
Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.
doi:10.1038/sj.bjc.6605374
PMCID: PMC2778540  PMID: 19826418
second-line chemotherapy; pancreatic cancer; irinotecan; oxaliplatin; gemcitabine
6.  Mental health insurance claims among spouses of frequent business travellers 
Objectives: Following up on two earlier publications showing increased psychological stress and psychosocial effects of travel on the business travellers this study investigated the health of spouses of business travellers.
Methods: Medical claims of spouses of Washington DC World Bank staff participating in the medical insurance programme in 1997–8 were reviewed. Only the first of each diagnosis with the ninth revision of the international classification of diseases (ICD-9) recorded for each person was included in this analysis. The claims were grouped into 28 diagnostic categories and subcategories.
Results: There were almost twice as many women as men among the 4630 identified spouses. Overall, male and female spouses of travellers filed claims for medical treatment at about a 16% higher rate than spouses of non-travellers. As hypothesised, a higher rate for psychological treatment was found in the spouses of international business travellers compared with non-travellers (men standardised rate ratios (RR)=1.55; women RR=1.37). For stress related psychological disorders the rates tripled for both female and male spouses of frequent travellers (≥ four missions/year) compared with those of non-travelling employees. An increased rate of claims among spouses of travellers versus non-travellers was also found for treatment for certain other diagnostic groups. Of these, diseases of the skin (men RR=2.93; women RR=1.41) and intestinal diseases (men RR=1.31; women RR=1.47) may have some association with the spouses' travel, whereas others, such as malignant neoplasms (men RR=1.97; women RR=0.79) are less likely to have such a relation.
Conclusion: The previously identified pattern of increased psychological disorders among business travellers is mirrored among their spouses. This finding underscores the permeable boundary between family relations and working life which earlier studies suggested, and it emphasises the need for concern within institutions and strategies for prevention.
doi:10.1136/oem.59.3.175
PMCID: PMC1763631  PMID: 11886948
7.  Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1 
Thorax  2000;55(2):121-125.
BACKGROUND—Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD.
METHODS—The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers.
RESULTS—No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group.
CONCLUSIONS—Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.


doi:10.1136/thorax.55.2.121
PMCID: PMC1745681  PMID: 10639528
8.  Pulmonary lymphangioleiomyomatosis in Korea 
Thorax  1999;54(7):618-621.
BACKGROUND—Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed.
METHODS—The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study.
RESULTS—All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (TLCO) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted TLCO/VA (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation.
CONCLUSIONS—As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.


PMCID: PMC1745515  PMID: 10377208
9.  Hypertrophic non-union of the first rib causing thoracic outlet syndrome: a case report. 
Journal of Korean Medical Science  2001;16(5):673-676.
We experienced a rare case of thoracic outlet syndrome caused by hypertrophic nonunion of the first rib. A diagnosis was made mainly upon provocative tests and imaging studies. Pain and tingling could be reproduced and the radial pulse obliterated by the hyperabduction test. Abundant callus formation on the posterior aspect of the first rib with fracture line was visible on plain radiograph. Two-dimensional computed tomography showed right thoracic outlet narrowing mainly caused by the mass-effect of the callus. Dynamic arteriographic studies revealed an external compression of the right subclavian artery and duplex ultrasonography demonstrated a reduction in right subclavian artery blood flow when the shoulder is in 90 degrees of abduction. Surgery was performed after the conservative management for three months which failed to relieve the patient of his complaints. Resection of the first rib via transaxillary approach was undergone uneventfully in combination with the myotomy of the scalenus anticus muscle. At postoperative one year follow up, the patient was free of symptoms, and had a full range of motion of the right shoulder with no evidence of arterial insufficiency.
PMCID: PMC3057587  PMID: 11641543
10.  The clinical characteristics of pulmonary alveolar proteinosis: experience at Seoul National University Hospital, and review of the literature. 
Journal of Korean Medical Science  1999;14(2):159-164.
Pulmonary alveolar proteinosis is such an extremely rare disease in Korea, that only a few cases have been reported. Meanwhile five cases were experienced at Seoul National University Hospital over ten years since 1987. We summarized the clinical characteristics and courses of them. Seven cases reported in the literature were included to add data about clinical characteristics and courses although only a few case reports mentioned patient's course. Middle aged male patients were mainly affected. No association with particular environmental or occupational exposure was identified. Dyspnea on exertion was the main symptom. Bilateral crackles were consistent, and bilateral parahilar hazy infiltrations on plain chest radiograph and ground glass opacity on high-resolution CT were characteristic. Superimposed infection was not identified in any patient at the time of diagnosis. Decreased diffusing capacity and hypoxia were present in almost every case. Whole lung lavage proved to be an effective therapeutic measure. The response to treatment was good. Long-term course of the disease, e.g. recurrence rate, is not yet known.
PMCID: PMC3054359  PMID: 10331561
11.  Isoniazid resistance and the point mutation of codon 463 of katG gene of Mycobacterium tuberculosis. 
It has long been known that almost all isoniazid (INH) resistant mycobacteria lose the catalase and peroxidase activities along with reduced or no virulence for guinea pigs. Recently resistance to INH has become known to be associated with mutations of katG gene encoding the HPI (Hydroperoxidase I) type catalase and peroxidase. Among these mutations, the point mutation of codon 463 of katG gene is found frequently, and is suggested as being associated with INH resistance. Therefore we performed this study in order to confirm the correlation between the point mutation of codon 463 of the katG gene and INH resistance of M. tuberculosis in Korea. Fifty isolates, 32 of which were resistant to INH, and 18 of which were sensitive to INH, were selected for this study. We used PCR-SSCP and RFLP analysis to detect the point mutation of the codon 463 of katG gene and confirmed the CGG (arginine) to CTG (leucine) mutation by direct sequencing analysis. Among 32 resistant isolates, 7 isolates (22%) had the same restriction pattern compared with that of the reference strain (H37Rv), and 25 isolates (78%) showed a different restriction pattern. Among 18 sensitive isolates, 7 isolates (39%) had the same restriction pattern compared with that of H37Rv, and 11 isolates (61%) showed a different restriction pattern. These results suggest that the CGG to CTG change of codon 463 of katG gene of M. tuberculosis may be a polymorphism not related with INH resistance.
PMCID: PMC3054244  PMID: 9170012
12.  La proteins from Drosophila melanogaster and Saccharomyces cerevisiae: a yeast homolog of the La autoantigen is dispensable for growth. 
Molecular and Cellular Biology  1994;14(8):5412-5424.
The human autoantigen La is a 50-kDa protein which binds to the 3' termini of virtually all nascent polymerase III transcripts. Experiments with mammalian transcription extracts have led to the proposal that the La protein is required for multiple rounds of transcription by RNA polymerase III (E. Gottlieb and J. A. Steitz, EMBO J. 8:851-861, 1989; R. J. Maraia, D. J. Kenan, and J. D. Keene, Mol. Cell. Biol. 14:2147-2158, 1994). Although La protein homologs have been identified in a variety of vertebrate species, the protein has not been identified in invertebrates. In order to begin a genetic analysis of La protein function, we have characterized homologs of the La protein in the fruit fly Drosophila melanogaster and the yeast Saccharomyces cerevisiae. We show that both the Drosophila and yeast La proteins are bound to precursors of polymerase III RNAs in vivo. The Drosophila and yeast proteins resemble the human La protein in their biochemical properties, as both proteins can be partially purified from cells by a procedure previously devised to purify the human protein. Similarly to vertebrate La proteins, the Drosophila and yeast homologs preferentially bind RNAs that terminate with a 3' hydroxyl. Despite the fact that the La protein is conserved between humans and Saccharomyces cerevisiae, yeast cells containing a null allele of the gene encoding the La protein are viable, suggesting that another protein(s) plays a functionally redundant role.
Images
PMCID: PMC359060  PMID: 8035818
13.  Double-stranded RNA unwinding and modifying activity is detected ubiquitously in primary tissues and cell lines. 
Molecular and Cellular Biology  1990;10(10):5586-5590.
A double-stranded RNA unwinding and modifying activity was found to be present in a wide range of tissues and cell types. The level of activity did not vary significantly with respect to the state of cell differentiation, cell cycle, or transformation. Thus, the unwinding and modifying activity, localized in the nucleus in somatic cells and capable of converting many adenosine residues to inosine, appears to be one of the housekeeping genes.
Images
PMCID: PMC361280  PMID: 2398905

Results 1-13 (13)