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1.  CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients 
British Journal of Cancer  2011;104(7):1126-1134.
Background:
We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.
Methods:
Among MGC patients (n=108), who received S-1 (40 mg m−2 b.i.d., days 1–14) and cisplatin (60 mg m−2, day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).
Results:
Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3% P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.
Conclusion:
Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.
doi:10.1038/bjc.2011.24
PMCID: PMC3068488  PMID: 21364592
cisplatin; CYP2A6; ERCC1; gastric cancer; polymorphism; S-1
2.  CT characteristics of a uterus-like mass in the sigmoid mesocolon 
The British Journal of Radiology  2011;84(997):e001-e003.
A uterus-like mass is a rare, benign extra-uterine tumour composed of smooth muscle and endometrium. The majority of uterus-like masses occur in the ovary. Rarely, uterus-like masses occur in the broad ligament, small bowel, small bowel mesentery or uterine cervix. Here, we report a case of a uterus-like mass in the sigmoid mesocolon. A well-defined, markedly enhanced soft-tissue mass with central cystic change and haemorrhage was observed on CT. The current report describes the CT characteristics of this sigmoid mesocolon uterus-like mass together with the differential diagnoses.
doi:10.1259/bjr/47170465
PMCID: PMC3473810  PMID: 21172956
3.  Synchronous double primary lung cancers of squamous and neuroendocrine type associated with cryptogenic fibrosing alveolitis. 
Thorax  1991;46(11):857-858.
A 72 year old man with simultaneously occurring squamous cell and neuroendocrine carcinomas in association with cryptogenic fibrosing alveolitis is reported. The tumours were separate and both were in the fibrotic area of the right lower lobe.
Images
PMCID: PMC1021046  PMID: 1771610
4.  Zymogram studies of human intestinal brush border and cytoplasmic peptidases. 
Gut  1979;20(11):987-991.
Zymogram studies of peptide hydrolases from the human intestinal brush border and cytoplasmic fractions produced multiple bands--that is, up to seven--while the brush border membrane produced only a single band of enzyme activity. With all of the substrates tested except L-leucyl-L-leucyl-L-leucine, a band having anodic mobility identical with that produced by the brush border enzymes was produced by the cytoplasmic enzymes. With L-trileucine as a substrate, no overlapping band was produced. This band in the cytoplasmic fraction was heat sensitive, while that in the brush border fraction was not. Thus it would appear that there is a single human intestinal brush border peptide hydrolase capable of hydrolysing a variety of di- and tri-peptides. This peptide hydrolases of the brush border and the cytoplasmic fraction of human intestine are distinct.
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PMCID: PMC1412683  PMID: 393572
5.  Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-κB-dependent iNOS and proinflammatory cytokines production 
British Journal of Pharmacology  2008;154(1):165-173.
Background and purpose:
Glycyrrhizae radix has been widely used as a cytoprotective, plant-derived medicine. We have identified a flavanoid, liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This research investigated the effects of liquiritigenin on the induction of inducible NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7 cells, and on paw oedema in rats.
Experimental approach:
iNOS expression was determined by western blotting, real-time reverse transcription-PCR and reporter gene analyses. Tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to assess NF-κB activation. The effect of liquiritigenin on acute inflammation in vivo was evaluated using carrageenan-induced paw oedema.
Key results:
Treatment of Raw264.7 cells with liquiritigenin caused inhibition of LPS-induced NF-κB DNA binding activity, due to repression of I-κBα phosphorylation and degradation. Liquiritigenin treatment prevented LPS from increasing the levels of iNOS protein and mRNA in a concentration-dependent manner. Liquiritigenin also suppressed the production of TNF-α, IL-1β and IL-6 from Raw264.7 cells after LPS. In rats, liquiritigenin treatment inhibited formation of paw oedema induced by carrageenan.
Conclusion and implications:
These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of NF-κB activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Our findings showing inhibition by liquiritigenin of paw oedema as well as inflammatory gene induction will help to understand the pharmacology and mode of action of liquiritigenin, and of the anti-inflammatory use of Glycyrrhizae radix.
doi:10.1038/bjp.2008.79
PMCID: PMC2438972  PMID: 18332856
liquiritigenin; iNOS; nuclear factor-κB; TNF-α; interleukin-1β; interleukin-6
6.  Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma 
British Journal of Cancer  2008;98(8):1305-1311.
We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m−2 b.i.d.) and docetaxel (25–40 mg m−2); MTD was 45 mg m−2 b.i.d. S-1/35 mg m−2 docetaxel and RD was 40 mg m−2 b.i.d. S-1/35 mg m−2 docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.
doi:10.1038/sj.bjc.6604312
PMCID: PMC2361699  PMID: 18362939
S-1; docetaxel; metastatic gastric carcinoma; phase I/II study
7.  Employment status and work-related difficulties in stomach cancer survivors compared with the general population 
British Journal of Cancer  2008;98(4):708-715.
Little was known about work situation and work-related difficulties, including housework after stomach cancer diagnosis. We aimed to compare employment status and work-related difficulties between stomach cancer survivors and the general population. We enrolled 408 stomach cancer survivors from two hospitals 28 months after diagnosis and 994 representative volunteers from the general population from 15 geographic districts. Working was defined as being employed (including self-employed) and nonworking as being retired or a homemaker. Nonworking was significantly higher among stomach cancer survivors (46.6%) than in the general population (36.5%). Compared with the general population, the survivors had more fatigue in performing both housework (adjusted odds ratio (aOR)=2.08; 95% confidence interval (95% CI)=1.01–4.29) and gainful work (aOR=4.02; 2.55–6.33). More cancer survivors had reduced working hours (aOR=1.42; 95% CI=4.60–28.35) and reduced work-related ability (aOR=6.11; 95% CI=3.64–10.27) than did the general population. The association of nonworking with older age and being female was significantly more positive for survivors than for the general population. Among survivors, poorer Eastern Cooperation Oncology Group Performance Status and receiving total gastrectomy were positively associated with nonworking. Stomach cancer survivors experienced more difficulties in both housework and gainful employment than did the general population. Our findings on stomach cancer survivors' work-related difficulties and the predictors of nonworking will help physicians guide patients towards more realistic postsurgical employment plans.
doi:10.1038/sj.bjc.6604236
PMCID: PMC2259191  PMID: 18283298
employment status; work; stomach cancer survivor; general population
8.  Bilateral primary pigmented nodular adrenocortical disease--a case of report describing a rare cause of Cushing's syndrome. 
A case of Cushing's syndrome due to bilateral pigmented nodular adrenal disease in a 35-year-old male is presented. The adrenals showed multiple, black, variable sized nodules. Histologically the cells contained lipofuscin and either had a clear cytoplasm or an eosinophilic cytoplasm with a prominent nucleus. Lymphocytic infiltration and fatty metaplasia within the nodules are two of the prominent histological features. There is extreme internodular atrophy which suggests that primary pigmented nodular adrenocortical disease is a non-adrenocorticotropic hormone dependent condition. Since the disorder appears to involve primarily the cortex of both adrenals, the treatment of choice is bilateral adrenalectomy followed by steroid replacement. The characteristic clinicopathological manifestations that separate this diagnosis from other types of adrenal disease are also discussed. This is the first reported case in Korea to be documented with the pertinent clinicopathological findings.
PMCID: PMC3054224  PMID: 7786440
9.  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
10.  Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma 
British Journal of Cancer  2006;94(10):1402-1406.
The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m−2) and irinotecan (70 mg m−2) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1–18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3–60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8–5.2 months) and overall survival was 8.2 months (95% CI, 5.8–10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.
doi:10.1038/sj.bjc.6603133
PMCID: PMC2361264  PMID: 16641896
docetaxel; gastric cancer; irinotecan
11.  Peptide hydrolases in the brush border and soluble fractions of small intestinal mucosa of rat and man 
Journal of Clinical Investigation  1972;51(6):1419-1430.
Peptide hydrolases, catalyzing the hydrolysis of 13 dipeptides and 5 tripeptides into their respective amino acids, were studied in small intestinal mucosa and other tissues, in man and in the rat.
Studies on the subcellular distribution of these enzymes showed enzyme activities in both the soluble and brush border fractions of the rat small intestinal mucosa, the former constituting 80-90% and the latter 10-15% of the total activity. Zymogram studies of peptide hydrolases, in both fractions, yielded multiple bands indicating multiple zones of enzyme activity. With most substrates a rather broad range of enzyme activities was observed in the soluble fraction differing only slightly from substrate to substrate, the exception being when L-leucyl-L-proline was used: this latter led to a zymogram pattern which was quite distinct. The synthetic substrates, L-leucyl-β-naphthylamide and L-leucinamide appeared to be hydrolyzed by two electrophoretically distinct enzymes, different from those hydrolyzing other leucyl-containing peptide substrates.
Zymogram patterns of the brush border membrane fraction were quite different from those of the soluble fraction of rat small intestine indicating that enzymes from the two sources may be different. No comparable human data were obtained.
Peptide hydrolases in the soluble fractions of various organs from the same species gave similar zymogram patterns, while those from the plasma membrane-bound fractions of different organs in the same species were peculiar to each organ. From these data, it is suggested that peptide hydrolases in the brush border and the soluble fractions of small intestine are distinct enzymes and may play different roles in cellular function.
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PMCID: PMC292279  PMID: 5024039
12.  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
13.  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
14.  Effect of high fat diet on insulin resistance: dietary fat versus visceral fat mass. 
Journal of Korean Medical Science  2001;16(4):386-390.
The purpose of the present study was to determine whether chronic high-fat diet (HF) induces insulin resistance independently of obesity. We randomly divided 40 rats into two groups and fed them either with a HF or with a high-carbohydrate diet (HC) for 8 weeks. Whole body glucose disappearance rate (Rd) was measured using a euglycemic hyperinsulinemic clamp. Firstly, we defined whether insulin resistance by HF was associated with obesity. Plasma glucose and triglyceride concentrations were significantly increased in HF. Rd was decreased (10.6+/-0.2 vs. 9.1+/-0.2 mg/kg/min in HC and HF, respectively) and the hepatic glucose output rate (HGO) was increased in HF (2.2+/-0.3 vs. 4.5+/-0.2 mg/kg/min in HC and HF, respectively). Rd was significantly correlated with %VF (p<0.01). These results implicate that visceral obesity is associated with insulin resistance induced by HF. In addition, to define whether dietary fat induces insulin resistance regardless of visceral obesity, we compared Rd and HGO between groups 1) after matching %VF in both groups and 2) using an ANCOVA to adjust for %VF. After matching %VF, Rd in HF was significantly decreased by 14% (p<0.001) and HGO was significantly increased by 110% (p<0.001). Furthermore, statistical analyses using an ANCOVA also showed Rd for HF was significantly decreased even after adjusting %VF. In conclusion, we suggest that dietary fat per se could induce insulin resistance in rats fed with chronic HF independently of obesity.
PMCID: PMC3054769  PMID: 11511781
15.  Change in activity of the sympathetic nervous system in diet-induced obese rats. 
Journal of Korean Medical Science  2000;15(6):635-640.
We investigated the change in activity of the sympathetic nervous system (SNS) in high-sucrose diet (HSD)-induced obese rats compared with controls. Power spectral analyses of R-R interval variability were performed to obtain the low frequency (LF, 0.04-0.699 Hz) and high frequency (HF, 0.7-3.0 Hz) powers. The percents of fat mass to body weight (%F/BW) and fat to muscle ratios (F/M) were significantly increased in HSD-fed rats. Plasma glucose, leptin, and triglyceride concentrations in rats fed with HSD were significantly increased. LF in normalized units (LFn), which represents both sympathetic and parasympathetic activities, was significantly increased whereas HF in normalized unit (HFn), which represents parasympathetic activity, was significantly decreased in HSD-fed rats. LF/HF, which represents sympathetic activity, was significantly increased in HSD-fed rats and was correlated with leptin (r=0.549, p<0.023), %F/BW (r=0.513, p<0.035), F/M (r=0.536, p<0.038), and triglyceride (r=0.497, p<0.042). When adjusted for leptin concentrations, however, LF/HF of HSD-fed rats was significantly decreased. In conclusion, HSD-induced obese rats showed increased LF/HF, which was significantly decreased by adjustment for leptin concentrations. We suggest that stimulating effect of leptin on SNS is reduced, which might play a role in induction of obesity by HSD.
PMCID: PMC3054699  PMID: 11194189
16.  Effects of BCG, lymphotoxin and bee venom on insulitis and development of IDDM in non-obese diabetic mice. 
Journal of Korean Medical Science  1999;14(6):648-652.
To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.
PMCID: PMC3054436  PMID: 10642943
17.  Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats. 
Journal of Korean Medical Science  1999;14(5):539-545.
In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration.
PMCID: PMC3054455  PMID: 10576150
18.  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
19.  Atypical pulmonary artery sling with diffuse-type pulmonary arteriovenous fistula. 
The case of a cyanotic infant with a rare combination of atypical pulmonary artery sling, imperforate anus, absence of the left kidney, interruption of the inferior vena cava, left side hemihypertrophy and diffuse-type pulmonary arteriovenous fistula is described. The clinical features were confusing, because of compounding abnormalities involving the respiratory tract and pulmonary circulation. The diagnostic approach to the etiology of cyanosis is discussed and the embryonic origin of pulmonary artery sling is reviewed.
PMCID: PMC3054176  PMID: 10102529
20.  Percutaneous transluminal coronary angioplasty in a child with Kawasaki disease. 
Journal of Korean Medical Science  1998;13(6):693-695.
A successful attempt at percutaneous transluminanl coronary angioplasty (PTCA) to relieve stenosis of the mid-portion of the left anterior descending artery was achieved in a 6-year 9-month old boy who had multiple coronary aneurysms and stenosis due to Kawasaki disease. Despite the progression of coronary stenosis he had been well except for the perfusion defect of the anterior wall of myocardium on 99mTc-MIBI SPECT with dipyridamole infusion until PTCA was carried out after 4-year 4-months of the onset of illness. The area of stenosis was 70% before PTCA and 20% after PTCA. No restenosis at the site of PTCA was observed on follow-up angiography at 26 months after PTCA. This successful attempt may indicate that this procedure should be considered early in subclinical stenosis to prevent ischemic cardiac damage.
PMCID: PMC3054539  PMID: 9886184
21.  Expression of osteopontin and osteonectin in breast cancer. 
Journal of Korean Medical Science  1998;13(6):652-657.
Osteopontin (OP) and osteonectin (ON) are bone matrix proteins produced by mammary and other cancers. These proteins may play a role in tumor invasion and metastasis through integrin-mediated signal transduction. We evaluated expressions of OP and ON in 253 resected infiltrating ductal carcinoma of the breast, using immunohistochemical staining and follow-up data. OP and ON were detected 87.4% and 54.2% of 253 cases, respectively. The OP and ON positive staining were localized in the cytoplasm of carcinoma cells. OP and ON did not correlate with various clinicopathological parameters, such as age, lymph node involvement, tumor size, histologic grade, expression of p53 and estrogen receptor (ER). In the multivariate model, lymph node involvement and histologic grade were statistically significant prognostic factors. Assessed by a log rank test, the 5-year-survival rates of OP and ON positive groups and their negative groups were not statistically different. In conclusion, OP and ON immunopositivity of infiltrating ductal carcinomas of the breast provide no additional prognostic information in this study.
PMCID: PMC3054552  PMID: 9886175
22.  Sinus histiocytosis with massive lymphadenopathy. Multiple skull involvements. 
Journal of Korean Medical Science  1998;13(4):423-427.
Sinus histiocytosis with massive lymphadenopathy is a non-neoplastic self-limiting disease of the bone marrow stem cell origin. It is characterized by painless, bilateral cervical lymphadenopathy accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. Extranodal involvement including bone is rare. The patient is a 45-year -old female with multiple punch out lesions on her skull. MRI findings included iso-signal intensity mass at the diploid space on T1 weighted image and on T2 weighted image, mild high signal intensity was obtained. Histologically, the lesion showed proliferation of histiocytes in the fibroblastic background with formation of reactive germinal centers and many plasma cells. The histiocytes show round nuclei and occasional nucleoli and abundant cytoplasms. In area, there is lymphocytophagocytosis. Immunohistochemically, the histiocytes were positive for S-100 protein and lysozyme.
PMCID: PMC3054428  PMID: 9741548
23.  Molecular genetic characterization of alternatively spliced CD44 transcripts in human stomach carcinoma. 
Journal of Korean Medical Science  1997;12(6):505-513.
CD44 is a member of cell surface glycoproteins which are involved in cell-matrix adhesion and tumor metastasis. Certain types of tumors express complex CD44 isoforms generated by alternative splicing of 2v-10v exons, and their expression appears to promote metastasis of tumor cells. Using a nested RT-PCR, we analyzed expression of CD44 variants in 26 stomach carcinoma, 21 matched normal tissues, and 2 carcinoma cell lines. We observed frequent and complex patterns of CD44 variant expression in tumor tissues. While exons 6v and 7v expression was detected in most normal and tumor tissues, exon 9v was most rarely detected. Exon 5v showed a significantly frequent expression in carcinoma, suggesting that its expression might contribute to the malignant progression. While exon 9v was frequently observed in diffuse-type tumors, the other 8 variant exons including 6v showed more frequent expression in intestinal-type tumors. Exons 9v and 10v were predominantly expressed in advanced tumor tissues and exon 8v was expressed more frequently in tumors of lymph node metastasis. We believe that series with a longer follow-up now need to be tested to clarify the association between CD44 splice variant expression and distant metastasis or long-term prognosis.
PMCID: PMC3054318  PMID: 9443088
24.  Extralobar pulmonary sequestration with an associated cyst of mixed bronchogenic and esophageal type--a case report. 
Journal of Korean Medical Science  1997;12(6):567-569.
We report an unusual case of extralobar pulmonary sequestration (ELS) with an associated cyst of mixed bronchogenic and esophageal type. A 58-year-old woman was incidentally found to have a 6 x 6 x 5 cm sized mass in the right superior mediastinum. The mass consisted of sequestrated pulmonary tissue and an unilocular cyst with a direct communication. The cyst could not be easily classified because it was lined by squamous or respiratory epithelium with two distinct muscle layers and bronchial glands. Bronchial cartilage was present in close proximity to the ELS. This unusual combination of ELS with a foregut cyst might be a part of bronchopulmonary foregut malformation, attributed to a common embryologic pathogenesis.
PMCID: PMC3054326  PMID: 9443099
25.  Pancreatic endocrine tumor admixed with a diffuse microcystic adenoma--a case report. 
Journal of Korean Medical Science  1997;12(5):469-472.
We report a case of pancreatic endocrine tumor admixed with a diffuse microcystic adenoma in a 67-year-old woman with a six months history of melena. Whipple's operation and near-total pancreatectomy were performed under the impression of a pancreatic cancer with duodenal invasion. The pancreas was enlarged and was entirely replaced by sponge-like tiny cysts, which were lined by a single layer of periodic acid Schiff positive cuboidal cells. Also encountered was a gray white solid area at the head portion which extended to the duodenum with an intraluminal polyp formation. The compact area was composed of solid and acinar structures of tumor cells, which showed a positive reaction for chromogranin A and neuron specific enolase, separated by delicate highly vascularized stroma. To the best of our knowledge, this is the first case report published with immunohistochemical studies to deal with a pancreatic endocrine tumor admixed with a diffuse microcystic adenoma.
PMCID: PMC3054307  PMID: 9364309

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