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Biomedical subjects

S W Lee

Publications and source records attributed to S W Lee.

At least 19 recordsLinked to original sources

Heparin-binding EGF-like growth factor is an early response gene to chemotherapy and contributes to chemotherapy resistance.

We have shown that one of the principle mechanisms of chemotherapy resistance involves the activation of nuclear factor kappa-B (NF-kappaB). In an effort to identify NF-kappaB-regulated chemotherapy response genes, we performed a microarray assay and observed that heparin-binding EGF-like growth factor (HB-EGF) was significantly upregulated by SN38 (a strong inducer of NF-kappaB activity) in colon cancer cells. Further studies revealed that HB-EGF was rapidly induced following a variety of chemotherapy treatments. Using RNA interference, we demonstrated that the chemotherapy-induced HB-EGF was largely dependent on activator protein-1 (AP-1) and NF-kappaB activation. Constitutive HB-EGF expression rescued AP-1/NF-kappaB small interfering RNA (siRNA) cells from chemotherapy-induced apoptosis. Meanwhile, we found that the enzymatic shedding of HB-EGF was also regulated by chemotherapy treatment, resulting in the elevated release of soluble HB-EGF from the cellular membrane. Induction of HB-EGF expression and ectodomain shedding synergistically led to robust epidermal growth factor receptor (EGFR) phosphorylation, whereas inhibition of HB-EGF expression by use of the HB-EGF inhibitor (CRM197) or siRNA resulted in the suppression of chemotherapy-induced EGFR phosphorylation. These results suggest that the chemotherapy-induced EGFR activation is regulated by HB-EGF. Finally, we demonstrated that overexpression of HB-EGF led to apoptotic resistance to chemotherapy, whereas suppression of HB-EGF expression by siRNA resulted in a dramatic increase in cell death. In summary, our study suggests that chemotherapy-induced HB-EGF activation represents a critical mechanism of inducible chemotherapy resistance. Therefore, therapeutic intervention aimed at inhibiting HB-EGF activity may be useful in cancer prevention and treatments.

Apoptosis↗

Oxidative stress induces a prolonged but reversible arrest in p53-null cancer cells, involving a Chk1-dependent G2 checkpoint.

Reactive oxygen species (ROS), the principal mediators of oxidative stress, induce responses such as apoptosis or permanent growth arrest/senescence in normal cells. Moreover, p53 activation itself contributes to ROS accumulation. Here we show that treatment of p53-null cancer cells with sublethal concentrations of ROS triggered an arrest with some morphological similarities to cellular senescence. Different from a classical senescent arrest in G(1), the ROS-induced arrest was predominantly in the G(2) phase of the cell cycle, and its establishment depended at least in part on an intact Chk1-dependent checkpoint. Chk1 remained phosphorylated only during the repair of double strand DNA breaks, after which Chk1 was inactivated, the G(2) arrest was suppressed, and some cells recovered their ability to proliferate. Inhibition of Chk1 by an RNAi approach resulted in an increase in cell death in p53-null cells, showing that the Chk1-dependent G(2) checkpoint protected cells that lacked a functional p53 pathway from oxidative stress. It has been proposed that the induction of a senescent-like phenotype by antineoplastic agents can contribute therapeutic efficacy. Our results indicate that oxidative stress-induced growth arrest of p53-null tumor cells cannot be equated with effective therapy owing to its reversibility and supports the concept that targeting Chk1 may enhance the effects of DNA-damaging agents on cancer progression in such tumors.

Animals↗

Methylation-induced silencing of ASC and the effect of expressed ASC on p53-mediated chemosensitivity in colorectal cancer.

Tumor suppressor p53 is known to play a crucial role in chemosensitivity in colorectal cancer. We previously demonstrated that an apoptosis-associated speck-like protein, ASC, is a p53-target gene which regulates p53-Bax mitochondrial apoptotic pathway. ASC is also known to be a target of methylation-induced gene silencing. An inactivation of ASC might thus cause resistance to chemotherapy, and if this is the case, then the expression of ASC would restore the chemosensitivity. The aim of this study was to clarify this hypothesis. ASC was methylated in 25% of all resected specimens in patients with colorectal cancer; however, ASC methylation did not always correspond to a lack of ASC protein. When expressed in colon cancer cells, in which ASC is absent due to methylation, ASC was found to enhance the chemosensitivity in a p53-dependent manner. In p53-null cells, ASC increased the p53-mediated cell death induced by p53-expressing adenovirus infection. Our data suggest that the methylation-induced silencing of ASC might cause resistance to p53-mediated chemosensitivity in colorectal cancer. The gene introduction of ASC may thus restore such chemosensitivity, and this modality may therefore be a useful new treatment strategy for colorectal cancer.

Antineoplastic Agents↗

The effects of Goami No. 2 rice, a natural fiber-rich rice, on body weight and lipid metabolism.

OBJECTIVE: Increased intake of dietary fiber reduces the risk of obesity and type 2 diabetes. We assessed the effects of a fiber-rich diet on body weight, adipokine concentrations, and the metabolism of glucose and lipids in non-obese and obese subjects in Korea, where rice is the main source of dietary carbohydrates. RESEARCH METHODS AND PROCEDURES: Eleven healthy, non-obese and 10 obese subjects completed two 4-week phases of individual isoenergetic food intake. During the control diet phase, subjects consumed standard rice; during the modified diet phase, subjects consumed equal proportions of fiber-rich Goami No. 2 rice and standard rice. We used a randomized, controlled, crossover study design with a washout period of 6 weeks between the two phases. RESULTS: After the modified diet phase, body weight was significantly lower in both the non-obese and obese subjects (non-obese, 57.0 +/- 2.9 vs. 56.1 +/- 2.8 kg, p = 0.001; obese, 67.7 +/- 2.1 vs. 65.7 +/- 2.0 kg, p < 0.001 for before vs. after). The BMI was significantly lower in obese subjects (26.9 +/- 0.5 vs. 26.0 +/- 0.6 kg/m2, p < 0.001). The modified diet was associated with lower serum triacylglycerol (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), and C-peptide (p < 0.05) concentrations in the obese subjects. DISCUSSION: These results indicate that fiber-rich Goami No. 2 rice has beneficial effects and may be therapeutically useful for obese subjects.

Adiponectin↗

Segmental dilatation of the ileum: A report of two cases.

Segmental dilatation of the ileum is one of the uncommon causes of intestinal obstruction. Preoperative diagnosis of segmental dilatation of the ileum is difficult. We report two cases of this condition that were diagnosed preoperatively by contrast studies.

Dilatation, Pathologic↗

Selective inhibition of polymorphonuclear neutrophils by resuscitative concentration of hypertonic saline.

OBJECTIVES: This study investigated the effect of hypertonic saline on the role of polymorphonuclear neutrophils (PMNs) in the inflammatory response and the effect of hypertonic saline infused at different phases in relation to an inflammatory stimulus. MATERIALS AND METHODS: PMNs were isolated from peripheral blood of healthy volunteers (Boyum's method) and cultured in three different media ([Na+] = 140 mmol/l, 180 mmol/l, and 200 mmol/l). PMNs were then stimulated with fMLP (N-formyl-methionyl-leucyl-phenylalanine) and H2O2 synthesis was quantified by flow cytometry at 5, 30, 60, 120, and 180 minutes. PMNs were treated with hypertonic saline before, simultaneously with, and after fMLP stimulation, and H2O2 synthesis quantified again. RESULTS: H2O2 synthesis was two or three times higher in fMLP stimulated than in non-stimulated PMNs, and it reached maximum level at 120 minutes. In the absence of fMLP stimulation, there was no significant difference between control and hypertonic saline with regard to activity of H2O2 synthesis. In the presence of fMLP stimulation, H2O2 synthesis significantly decreased in PMNs treated with hypertonic saline. There was no significant difference between the two hypertonic saline solutions ([Na+] = 180 mmol/l and 200 mmol/l) with regard to H2O2 synthesis. However, H2O2 synthesis decreased in PMNs treated with hypertonic saline before and simultaneously with fMLP stimulation, but was not significantly decreased in the cells treated with hypertonic saline after fMLP stimulation. CONCLUSIONS: Hypertonic saline appears to decrease H2O2 in stimulated neutrophils. This may be a further beneficial role of hypertonic saline when used clinically as an early resuscitation fluid.

Analysis of Variance↗

Diagnostic radiopacity and hepatotoxicity following chloroform ingestion: a case report.

BACKGROUND: Diagnostic imaging can help in the management of toxicologic emergencies. The authors report on a patient who presented to the emergency department with coma and suppressed respirations after ingestion of an unknown substance. METHODS: Ingestion of chloroform with radiopaque material in the bowel on abdominal radiograph was documented. The patient was treated with haemoperfusion, activated charcoal, and laxatives to decrease the toxicities. RESULTS: Hepatotoxicity occurred on post-ingestion day 3 and elevation of liver enzymes reached peak levels on post-ingestion day 5. The patient received N-acetylsystein and supportive care during hospitalisation. The patient improved from hepatic dysfunction and was discharged without complication on post-ingestion day 11. CONCLUSION: Radiographic studies in toxicology may confirm a diagnosis and assist in therapeutic intervention.

Adult↗

Predictors of serious bacterial infection in children aged 3 to 36 months with fever without source.

INTRODUCTION: Children commonly present with fever without source yet there is no reliable and consistent method of identifying those at risk of serious bacterial infection. In this study, we sought to identify predictors of serious bacterial infection in children aged between three to 36 months with fever without source. METHODS: Inpatient records of all children aged three to 36 months admitted from the Emergency Department of Singapore's main paediatric hospital between October 2001 to February 2002 with International Classification of Diseases (ninth revision) diagnosis codes 038 (septicaemia), 079 (viral fever), or 780 (pyrexia of unknown origin), were retrieved and reviewed. Patients identified as having fever without source were enrolled. RESULTS: Of 86 enrolled children, 17 (19.8 percent) had serious bacterial infection. Duration of fever and white blood cell count were found to be significant predictors. Children with white blood cell count equal to or greater than 16,000/cubic mm had 6.9 times (95 percent confidence interval [CI] is 1.7 to 28.4) increased risk of serious bacterial infection, while children with fever of duration exceeding three days before presentation had 3.8 times (95 percent CI is 1.1 to 13.1) increased risk of serious bacterial infection. A combination of white blood cell count less than 16,000/cubic mm and duration of fever three days or less had a negative predictive value of 1.0 (95 percent CI is 0.88 to 1.0) and a sensitivity of 1.0 (95 percent CI is 0.82 to 1.0). CONCLUSION: The two identified predictors offer an estimate of the risk of serious bacterial infection in children aged three to 36 months with fever without source.

Bacterial Infections↗

OK-432 sclerotherapy of plunging ranula in 21 patients: it can be a substitute for surgery.

BACKGROUND AND PURPOSE: Although first-choice therapy for the ranula is surgery, this choice presents technical difficulties and frequent recurrences because of insufficient surgery. We evaluated the efficacy of OK-432 sclerosis of the plunging ranula as a substitute for surgery. METHODS: Twenty-one patients with plunging ranula were treated with intralesional injection of OK-432. The liquid content of the ranula was aspirated as much as possible, after which OK-432 solution was injected in the same volumes as that drawn out. Patients were followed on sonography or CT. RESULTS: Seven (33.3%) patients with plunging ranulas showed total shrinkage and resolution, and 4 (19%) patients showed near-total shrinkage (more than 90% of the volume). Four (19%) patients revealed marked shrinkage (more than 70% of the volume), and 3 (14.3%) patients showed partial shrinkage (less than 70% of the volume). Three (14.3%) patients showed recurrence after total shrinkage 1 month after injection. The overall recurrence rate after each injection was 47% (16 of 34 injections in 21 patients), but the recurrence rate after the last sclerotherapy was only 14%. There were no serious side effects except for fever lasting 2-3 days (12 patients) and swelling (10 patients) for 3-5 days. Mild odynophagia for 1-2 days was also noted in 7 patients, and there was 1 severe case of odynophagia. CONCLUSION: OK-432 sclerotherapy of plunging ranula is a safe and potentially curative procedure that may be used as a primary treatment for plunging ranula before considering surgery.

Adolescent↗

Rerupture following endovascular treatment for dissecting aneurysm of distal anterior inferior cerebellar artery with parent artery preservation: retreatment by parent artery occlusion with Guglielmi detachable coils.

Distal anterior inferior cerebellar artery (AICA) aneurysms are rare and most cases have been treated surgically by clipping, wrapping or trapping. We recently treated this 20-year-old male patient by an endovascular technique. At first, he was treated by intra-aneurysmal embolisation with parent artery preservation. But he presented with rerupture 1 month after embolisation. Follow-up angiography revealed the regrowth of the aneurysm, which was considered as a dissecting aneurysm. We performed occlusion of the AICA just proximal to the aneurysm to prevent fatal rebleeding. He gradually improved and his level of consciousness fully recovered. At 2 year follow up, he had no neurological deficits. We suggest that embolisation of distal AICA aneurysm with parent artery occlusion may be safe and a simple method in the treatment of distal AICA aneurysms.

Adult↗

Post-interventional immunosuppressive treatment and vascular restenosis in Takayasu's arteritis.

OBJECTIVE: To investigate the outcome of vascular interventions and the effect of post-interventional immunosuppressive treatment on the occurrence of vascular restenosis in patients with Takayasu's arteritis (TA). METHODS: Forty-two patients with TA who had undergone vascular intervention and had serial angiographies before and after intervention were enrolled. The demographic and clinical data were collected at the time when the interventions were performed, and the intervention modalities and post-interventional medical treatments were evaluated. RESULTS: Sixty-three interventions were performed in 42 patients. Twenty (31.7%) interventions restenosed 24.0 +/- 21.9 months after intervention; the likelihood decreasing as time passed. Estimates of arterial patency after intervention were 90.1% at 1 yr, 75.5% at 2 yr, 68.4% at 3 yr, 61.6% at 5 yr and 49.3% at 10 yr. According to the log rank test, interventions that were performed during the stable stage of the disease (P = 0.039) and those that were followed by treatment with glucocorticoids and immunosuppressive agents (P = 0.044) were independent variables for the maintenance of arterial patency. Their hazard ratios were 0.30 and 0.41, respectively. CONCLUSION: Restenosis occurred in 31.7% of TA patients after intervention. A lower restenosis rate was observed when the vascular interventions were performed at the stable stage and when post-interventional immunosuppressive treatment was implemented.

Adolescent↗

Serum cytokine profiles and their correlations with disease activity in Takayasu's arteritis.

OBJECTIVE: To investigate serum profiles of inflammatory cytokines in patients with Takayasu's arteritis (TA) and to determine their correlations with disease activity of TA. METHODS: Forty-nine patients with TA and 12 age- and sex-matched controls were studied. Blood samples were obtained and were divided into active and stable disease groups. Paired blood samples were available in 19 patients at the active stage before treatment and at the remitted stage after treatment. Serum tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-6, IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum TNF-alpha, IL-6 and IL-18 levels of patients with TA were significantly higher than those of controls (P<0.05), but IFN-gamma and IL-12 levels were not. Serum IL-6 and IL-18 levels were significantly higher in the active disease group than in the stable disease group (P<0.05), but the levels of TNF-alpha were not different between the groups. In the 19 patients with paired samples, serum IL-18 levels at the remitted stage after treatment were significantly decreased compared with the active stage before treatment (P<0.001). The changes in IL-18 levels between active and remitted stages correlated well with changes in erythrocyte sedimentation rate (P<0.001). CONCLUSION: Serum IL-18 and IL-6 levels were elevated in patients with TA, especially in those with active disease. Serum IL-18 levels correlated well with disease activity of TA. These results suggest that IL-6 and IL-18 might contribute to the pathogenesis of TA and that IL-18 could be a useful marker for monitoring disease activity of TA.

Adult↗

Intraoperative carbon dioxide colonoscopy: a safe insufflation alternative for locating colonic lesions during laparoscopic surgery.

BACKGROUND: Intraoperative colonoscopy (IOC) is useful for locating colonic pathologies during laparoscopy, but bowel distention compromises the subsequent visualization and procedure. Carbon dioxide (CO2), with its rapid absorption, has been proved effective for alleviating bowel distention in ambulatory settings. Its intraoperative role, however, has never been studied. This study aimed to assess the feasibility, safety, and advantages of CO2-insufflated IOC during laparoscopy. METHODS: For this study, CO2-insufflated IOC was performed for 20 patients under CO2 pneumoperitoneum. Parameters, including end-tidal CO2 (ETCO2) and minute volume, were prospectively registered. Time until resolution of bowel distention was determined by laparoscopic evaluation. RESULTS: All lesions were located by CO2-insufflated IOC in 15 min. During IOC, ETCO2 increased, but remained within normal values, and was quickly compensated with minimal hyperventilation. Bowel distention totally disappeared in 21 min, allowing immediate initiation of laparoscopic procedures under adequate visualization. CONCLUSIONS: The findings show that CO2-insufflated IOC during laparoscopy is feasible, safe, and of practical value for minimizing bowel distention without impeding the subsequent visualization and procedure.

Adult↗

Delayed occurrence of intracranial supratentorial chondroma following compound depressed skull fracture.

We describe an exceptional case of a frontal convexity chondroma arising at the site of a compound depressed skull fracture operated on 12 years earlier. We conclude that intracranial chondroma should be included in the differential diagnosis of a calcified mass for the patients who had had a compound, depressed skull fracture along the suture line, especially in cases of dural laceration by the fragmented bone.

Adolescent↗

Co-combustion performance of poultry wastes and natural gas in the advanced Swirling Fluidized Bed Combustor (SFBC).

Co-combustion of poultry wastes with natural gas in an advanced Swirling Fluidized Bed Combustor (SFBC) has been carried out to investigate the performance of poultry wastes combustion. Wastes burnt were poultry litter, poultry manure and sawdust. This paper presents the effect of three different wastes, excess air ratio, and secondary/total air ratio on the combustion characteristics. These characteristics include temperature distributions, carbon combustion efficiency, major gaseous pollutants emissions and heat recovery efficiency. The results indicate that, with the given moisture and ash contents in wastes, the excess air and the secondary air play important roles in achieving stable combustion. The carbon combustion efficiency could increase by 8-10% when the excess air is increased to 25% with the secondary air being at 20% and having a low injection height. However, the carbon combustion efficiency for the sawdust, which is 92% on average, is much higher than that of the poultry litter and manure, which is 81% and 76% on average, respectively. Differences regarding temperature distribution and pollutants emission were also observed with different combinations of the excess air, the secondary air and the secondary air injection height. The NO(x) emission was very low even though the materials contain high levels of nitrogen. In addition, the heat recovery efficiency aiming at the commercial use of the SFBC system for the farm industries was also evaluated.

Agriculture↗

Simultaneous midline laser glossectomy with palatopharyngeal surgery for obstructive sleep apnoea syndrome.

We investigate the outcome of performing tongue base reduction surgery and palatopharyngeal surgery in a single stage to determine whether the same-stage midline laser glossectomy (MLG) with extended uvulopalatal flap (EUPF) for obstructive sleep apnoea syndrome (OSAS) is a safe and effective procedure. Six male patients with a history of severe OSAS were recruited into the retrospective study. They were the first patients to undergo the MLG with EUPF procedure. Patients were identified to have retropalatal and hypopharyngeal sites of obstruction on the basis of fiberoptic endoscopy with Muller's manoeuvre and three-dimensional computerised tomography. No significant adverse events occurred. The follow-up polysomnography (6-month follow-up) revealed that the mean respiratory disturbance index from 50.7 to 11.6, snoring index from 230.9 to 137.3 and the minimal oxygen saturation from 76.3 to 88.8. This study confirms that the same-stage MLG with EUPF for OSAS is a safe and effective procedure.

Adult↗

Three cases of adenocarcinoma following restorative proctocolectomy with hand-sewn anastomosis for ulcerative colitis: a review of reported cases in the literature.

Restorative proctocolectomy (RPC) has been accepted as optimal surgical therapy for most patients with ulcerative colitis. The occurrence of adenocarcinoma adjacent to the ileoanal anastomotic site for ulcerative colitis is a serious but rare outcome. There are 16 reported cases. We report three additional cases and review previous cases in the literature.

Adenocarcinoma↗

Acute mediastinitis resulting from an unsuspected fish bone--case report.

Acute mediastinitis is a serious medical condition with a mortality rate from 30 to 40% or even higher. Early diagnosis with prompt and aggressive treatment is essential to prevent its rapid progression. Severe odynophagia and respiratory distress with positive neck or chest findings should raise suspicion of mediastinitis. We report a rare case of acute mediastinitis secondary to the unexpected migration of an impacted fish bone from the esophagus.

Acute Disease↗