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Biomedical subjects

H Y Jung

Publications and source records attributed to H Y Jung.

At least 19 recordsLinked to original sources

Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of capecitabine plus irinotecan in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received oral capecitabine 1000 mg m(-2) twice daily from day 1 to 14 and intravenous irinotecan 100 mg m(-2) on days 1 and 8, based on a 3-week cycle. Forty-one patients were enrolled in the current study, among whom 38 were assessable for efficacy and 40 assessable for toxicity. Three complete responses and 16 partial responses were confirmed, giving an overall response rate of 46.3%. At a median follow-up of 269 days, the median time to progression and overall survival were 5.1 and 8.6 months, respectively. Grade 3/4 neutropenia occurred in four patients and grade 3 febrile neutropenia was observed in two patients. Grade 3 diarrhoea and grade 2 hand-foot syndrome occurred in six patients and eight patients, respectively. The combination of capecitabine and irinotecan was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as one of first-line treatment options for advanced gastric cancer.

Adenocarcinoma↗

Cortical control of voluntary blinking: a transcranial magnetic stimulation study.

OBJECTIVE: To investigate cortical regions related to voluntary blinking. METHODS: Transcranial magnetic stimulation (TMS) was applied to the facial motor cortex (M1) and the midline frontal region (Fz) in 10 healthy subjects with eyes opened and closed. Motor-evoked potentials were recorded from the orbicularis oculi (OOC), orbicularis oris (OOR), abductor digiti minimi and tibialis anterior using surface and needle electromyography electrodes. Facial M waves and blink reflex were measured using supramaximal electrical stimulation of the facial and supraorbital nerves. RESULTS: TMS at Fz elicited 3 waves in OOC with no response in other tested muscles except for the early wave in OOR. Facial M1 stimulation produced only early and late waves. Because of their latencies, shapes, and relationship to coil position and stimulation intensity, early and late waves appeared to be analogous to the facial M wave and R1 component of the blink reflex. The intermediate wave at 6-8 ms latency was elicited in OOC by Fz stimulation with eyes closed. CONCLUSIONS: Since its latency matches the central conduction time of other cranial muscles and it has characteristic of muscle activation-related facilitation, the intermediate wave is presumably related to cortical stimulation. This result provides evidence that the cortical center for the upper facial movements, including blinking, is not principally located in the facial M1, but rather in the mesial frontal region.

Adult↗

Flumazenil does not affect intracortical motor excitability in humans: a transcranial magnetic stimulation study.

OBJECTIVE: The motor cortex may be subject to tonic inhibitory drive. One inhibitory mechanism is supported by activity at benzodiazepine (BZP) receptors. In this study we investigate whether or not the BZP antagonist, flumazenil, increases cortical motor excitability in humans. METHODS: Eight healthy subjects received a 1 mg intravenous (i.v.) loading dose of flumazenil followed by a 0.5 mg i.v. infusion over the next 30 min. Before, during, and 1 h after flumazenil infusion, we measured cortical motor excitability using transcranial magnetic stimulation (TMS). This included resting motor threshold (rMT), paired-pulse measurements of intracortical inhibition and facilitation (ICI and ICF), recruitment curve (RC), and silent period (SP). We also measured F response and compound muscle action potential (CMAP) with peripheral nerve stimulation. The study was carried out using a randomized, double-blind crossover design controlled with a saline infusion. RESULTS: None of the measures of cortical or peripheral excitability were significantly affected by drug administration. CONCLUSIONS: Our findings suggest that flumazenil has no effect on cortical motor excitability in normal humans. SIGNIFICANCE: There does not appear to be any tonic activity at benzodiazepine receptors in the normal resting human motor cortex.

Action Potentials↗

Effect of rebamipide in treatment of Helicobacter pylori-associated duodenal ulcer: attenuation of chemokine expression and nitrosative damage.

Production of cytokines along with increased activity of nitric oxide synthase has been implicated as one of the contributing mechanisms of Helicobacter pylori-mediated gastroduodenal diseases. We aimed to evaluate the effect of rebamipide in treating Helicobacter pylori-associated duodenal ulcers in terms of cytokine production and nitrosative damage of the gastric mucosa. In patients with duodenal ulcers, rebamipide or placebo were given randomly after eradication. Mucosal cytokine production was measured by enzyme linked immunoassay, and nitrotyrosine immunoexpression was measured by immunohistochemistry. The inflammatory activity and degree of neutrophil infiltration were graded accordingly. The mucosal production of RANTES, interleukin-8, and TNF-alpha showed a significant decrease after eradication in patients with rebamipide after-treatment. The nitrotyrosine immunoreactivity of gastric epithelium was significantly decreased in the rebamipide group. Rebamipide treatment after eradication resulted in a significant reduction in chemokine production along with nitrotyrosine immunoexpression in Helicobacter pylori-associated duodenal ulcers.

Adult↗

Effect of levetiracetam on human corticospinal excitability.

OBJECTIVE: To investigate whether levetiracetam (LTC) alters corticospinal excitability in humans. BACKGROUND: Although the antiepileptic activity of LTC is well recognized, its mechanism of action has yet to be determined. Transcranial magnetic stimulation (TMS) has been used to investigate the pharmacologic effects of various antiepileptic drugs on human corticospinal excitability. METHODS: The authors performed TMS before and after double-blind administration of 3000 mg LTC or placebo in six healthy volunteers. TMS measurements included resting and active motor threshold (MT), recruitment curve of motor-evoked potential amplitudes, intracortical inhibition, and facilitation using the paired-pulse technique and silent period. F-wave and compound muscle action potential (CMAP) were also measured. RESULTS: In recruitment curve measurements, motor-evoked potential amplitude was reduced for LTC with high stimulation intensity (130% and 140% of resting MT) compared with placebo (p < 0.05 and p < 0.01), but not with relatively low stimulation intensity (110% and 120%). The changes in other TMS measurements as well as F-wave and CMAP after LTC did not differ significantly from those observed after placebo administration. CONCLUSION: These results suggest that LTC reduces the corticospinal neuronal response to magnetic stimulation, preferentially affecting less excitable neurons. The lack of change in F-wave and CMAP suggests that this effect is mainly derived from the motor cortex.

Adult↗

Action potential bursting in subicular pyramidal neurons is driven by a calcium tail current.

Subiculum is the primary output area of the hippocampus and serves as a key relay center in the process of memory formation and retrieval. A majority of subicular pyramidal neurons communicate via bursts of action potentials, a mode of signaling that may enhance the fidelity of information transfer and synaptic plasticity or contribute to epilepsy when unchecked. In the present study, we show that a Ca(2+) tail current drives bursting in subicular pyramidal neurons. An action potential activates voltage-activated Ca(2+) channels, which deactivate slowly enough during action potential repolarization to produce an afterdepolarization that triggers subsequent action potentials in the burst. The Ca(2+) channels underlying bursting are located primarily near the soma, and the amplitude of Ca(2+) tail currents correlates with the strength of bursting across cells. Multiple channel subtypes contribute to Ca(2+) tail current, but the need for an action potential to produce the slow depolarization suggests a central role for high-voltage-activated Ca(2+) channels in subicular neuron bursting.

Action Potentials↗

Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer.

PURPOSE: To evaluate the local control rates, survival rates, and patterns of failure for esophageal cancer patients receiving preoperative concurrent chemotherapy and hyperfractionated radiotherapy followed by esophagectomy. METHODS AND MATERIALS: From May 1993 through January 1997, 94 patients with resectable esophageal cancers received continuous hyperfractionated radiation (4,800 cGy/40 fx/4 weeks), with concurrent FP chemotherapy (5-FU 1 g/m(2)/day, days 2-6, 30-34, CDDP 60 mg/m(2)/day, days 1, 29) followed by esophagectomy 3-4 weeks later. If there was evidence of disease progression on preoperative re-evaluation work-up, or if the patient refused surgery, definitive chemoradiotherapy was delivered. Minimum follow-up time was 2 years. RESULTS; All patients successfully completed preoperative treatment and were then followed until death. Fifty-three patients received surgical resection, and another 30 were treated with definitive chemoradiotherapy. Eleven patients did not receive further treatment. Among 91 patients who received clinical reevaluation, we observed 35 having clinical complete response (CR) (38.5%). Pathologic CR rate was 49% (26 patients). Overall survival rate was 59.8% at 2 years and 40.3% at 5 years. Median survival time was 32 months. In 83 patients who were treated with surgery or definitive chemoradiotherapy, the esophagectomy group showed significantly higher survival, disease-free survival, and local disease-free survival rates than those in the definitive chemoradiation group. CONCLUSION: Preoperative chemoradiotherapy in this trial showed improved clinical and pathologic tumor response and survival when compared to historical results. Patients who underwent esophagectomy following chemoradiation showed decreased local recurrence and improved survival and disease-free survival rates compared to the definitive chemoradiation group.

Aged↗

CpG island methylation in premalignant stages of gastric carcinoma.

There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.

Adaptor Proteins, Signal Transducing↗

The antioxidant effect of rebamipide on oxygen free radical production by H. pylori-activated human neutrophils: in comparison with N-acetylcysteine, ascorbic acid and glutathione.

Helicobacter pylori(H. pylori)-activated neutrophils produce the oxygen-derived free radicals (OFRs) which play an important role in gastric mucosal cell damage. Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid) is an antiulcer compound, which protects gastric mucosa against OFR-mediated injury. In order to investigate the effects of rebamipide on OFR production and to compare the antioxidant activity of rebamipide with those of three known antioxidants, N-acetylcysteine (AC), ascorbic acid (Vit C) and glutathione (GSH), the antioxidant activities were determined by luminol-dependent chemiluminescence (ChL) assay and pyrogallol autoxidation assay. The ChL value was markedly elevated immediately after the addition of H. pylori into the medium containing neutrophils. The antioxidant activity of 1.0 mM rebamipide was greater than that of 0.1 mM rebamipide in the luminol-dependent ChL assay, while in the pyrogallol autoxidation assay, the antioxidant activity of 1.0 mM rebamipide was similar to that of 0.1 mM rebamipide. Rebamipide inhibited OFR generation in the pyrogallol autoxidation assay, with the potency being in the order of GSH > Vit C > rebamipide > AC. In the luminol-dependent ChL assay, the antioxidant activity of rebamipide was the greatest among them. These results indicate that rebamipide is a potent antioxidant and scavenges OFRs produced by H. pylori effectively in luminol-dependent ChL assays.

Acetylcysteine↗

Source of errors in the evaluation of early rectal cancer by endoluminal ultrasonography.

PURPOSE: Although preoperative evaluation of early rectal cancers can be done by endoluminal sonography and by means of colonoscopic findings, it is still controversial whether endoluminal sonography can effectively discriminate mucosal from submucosal lesions. This study was performed to verify objective causes of errors in the evaluation of early rectal cancer (T0/1) using a review of videotaped endoluminal sonography images. METHODS: Eighty-nine patients with suspected early rectal cancer on endoluminal sonography were included. Two different scanners with appropriate probes were used according to tumor location, i.e., transrectal ultrasonography was used to scan up to 8 cm of the rectum above the anal verge, whereas endoscopic ultrasonography was used to assess higher lesions. Endoluminal sonography images were correlated with histologic infiltration and were reevaluated carefully to identify sources of errors. RESULTS: Sensitivity and specificity were 83.1 and 96.5 percent, respectively, for tumor staging, whereas sensitivity was very low compared with specificity (16.7 vs. 90.2 percent) for metastatic lymph nodes. Endoluminal sonography images showed irregularity of the underlying tumor border (P < 0.01) and hypoechoic blurring or cutoff of the inner and outer hypoechoic layers (P < 0.001), all of which closely correlated with histologic infiltration of tumor cells. Overstaging occurred more than twice as often as understaging in tumor reevaluation (14 vs. 5 occurrences). In contrast to tumors, lymph nodes showed a similar amount of both overstaging (four cases) and understaging (five cases). The sources of errors were summarized as five types: false instrumentation, interpretive errors, anatomic defects, imaging failure, and inevitable errors. CONCLUSIONS: Because false instrumentation, interpretive errors, and anatomic defects were considered preventable, 23 (82.1 percent) of the 28 errors might have been avoided. Therefore, a clear image by endoluminal sonography can effectively distinguish mucosal from submucosal lesions in early rectal cancer.

Diagnosis, Differential↗

Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea.

BACKGROUND: Helicobacter pylori infection occurs throughout the world and causes gastroduodenal diseases in all age groups. The prevalence of H. pylori infection varies between countries and races. The aim of this study was to evaluate the seroprevalence of H. pylori infection in asymptomatic healthy people in South Korea. METHODS: From March 1998 to October 1998, 5732 asymptomatic subjects who responded to the self-assessment questionnaires from 54 hospitals in South Korea were enrolled in this study. The serum levels of antibodies for H. pylori immunoglobulinG were measured by using an ELISA test. RESULTS: The overall seroprevalence of H. pylori infection was 46.6% and there was no statistical difference between males (47.2%) and females (45.9%). In adults, a significant difference was observed between genders. According to the geographic areas, the high prevalent provinces were Kangwon (53.4%), Cheju (52.9%) and Cholla province (50.6%); Seoul (41.9%) was the lowest prevalent area. The seroprevalence increased with age and was highest when patients were aged in their 40s (78.5%). The characteristic feature of our study was that the infection rate was steeply increased in three age groups (10-12 year olds, 16-19 year olds and those aged in their 20s). In Seoul, there was no difference in the prevalence rate among the districts studied. CONCLUSIONS: This nation-wide seroprevalence of H. pylori infection in South Korea was 46.6%, which showed the transition from a developing country to a developed country. More studies on the epidemiological factors and the route of transmission of H. pylori infection should be warranted.

Adolescent↗

Methylation of the hMLH1 promoter in multiple gastric carcinomas with microsatellite instability.

Hypermethylation of the hMLH1 promoter is observed in the majority of sporadic gastric carcinomas with high frequency microsatellite instability (MSI), and it contributes to the genesis of MSI-positive gastric carcinoma. Multiple gastric carcinoma is known to have a higher frequency of MSI positivity than single gastric carcinoma. However, the molecular basis of MSI in these tumors remains obscure. We investigated the role of hMLH1 promoter hypermethylation in the genesis of multiple gastric carcinoma with MSI. We analyzed 33 tumors from 15 patients with multiple gastric carcinoma (12 double tumors and three triple tumors) for MSI, expression of hMLH1 and hMSH2, and hypermethylation of hMLH1 and hMSH2 promoters. High frequency MSI was found in seven out of 33 tumors (21%) in five out of 15 patients (33%). All of the tumors with high frequency MSI had a lack of hMLH1 expression, with the presence of hMSH2 expression, while all the tumors with no MSI or low frequency MSI were positive for both hMLH1 and hMSH2. All of the tumors with no expression of hMLH1 had hMLH1 hypermethylation, whereas hMLH1 hypermethylation was observed in two out of 26 (8%) tumors with no or low frequency MSI. None of the tumors showed hMSH2 hypermethylation. These results suggest that epigenetic changes in the hMLH1 promoter account for the genesis of multiple gastric carcinoma with high frequency MSI.

Adaptor Proteins, Signal Transducing↗

Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract caused by an abnormal and uncontrolled immune response to one or more normally occurring gut constituents. AIM: Given the effects of transforming growth factor beta1 (TGF-beta1) on both the immune system and extracellular matrix, we postulated that alterations in TGF-beta signalling in intestinal epithelial cells may play an important role in the development of IBD. METHODS: TGF-beta signalling was inactivated in mouse intestine by expressing a dominant negative mutant form of the TGF-beta type II receptor under the control of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF-dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia, and anal prolapse when not maintained under specific pathogen free (SPF) conditions. Under SPF conditions we induced colitis by mixing dextran sodium sulphate (DSS) in drinking water to examine the significance of loss of TGF-beta signalling in the pathogenesis of IBD. RESULTS: Transgenic mice showed increased susceptibility to DSS induced IBD, and elicited increased expression of major histocompatibility complex class II, generation of autoantibodies against intestinal goblet cells, and increased activity of matrix metalloproteinase in intestinal epithelial cells compared with wild-type littermates challenged with DSS. CONCLUSIONS: Deficiency of TGF-beta signalling specifically in the intestine contributes to the development of IBD. Maintenance of TGF-beta signalling may be important in regulating immune homeostasis in the intestine

Animals↗

PhyloDraw: a phylogenetic tree drawing system.

UNLABELLED: PhyloDraw is a unified viewing tool for phylogenetic trees. PhyloDraw supports various kinds of multi-alignment formats (Dialign2, Clustal-W, Phylip format, NEXUS, MEGA, and pairwise distance matrix) and visualizes various kinds of tree diagrams, e.g. rectangular cladogram, slanted cladogram, phylogram, unrooted tree, and radial tree. By using several control parameters, users can easily and interactively manipulate the shape of phylogenetic trees. This program can export the final tree layout to BMP (bitmap image format) and PostScript. AVAILABILITY: http://pearl.cs.pusan.ac.kr/phylodraw/ CONTACT: jhchoi@pearl.cs.pusan.ac.kr

Computational Biology↗

Covered retrievable expandable nitinol stents in patients with benign esophageal strictures: initial experience.

PURPOSE: To investigate the safety and clinical effectiveness of covered retrievable expandable nitinol stents in 25 patients with a benign esophageal stricture. MATERIALS AND METHODS: Under fluoroscopic guidance, covered retrievable expandable nitinol stents were placed in 25 patients with a benign esophageal stricture and were removed with a retrieval hook 1-8 weeks later. RESULTS: Stent placement was successful in all patients, with no procedural complications. After stent placement, all patients could ingest solid food. The stents were successfully removed from all but two patients. One patient passed the stent via the rectum, and the other regurgitated a high cervical stent. After stent removal, one patient developed a small esophagobronchial fistula, which spontaneously sealed within 1 week of stent removal. After stent removal or migration, all patients could ingest solid food. During follow-up (mean, 13 months; range, 2-25 months) after stent removal or migration, 12 patients maintained their improvement in dysphagia and needed no further treatment. Thirteen patients with recurrence were treated by means of repeat balloon dilation. CONCLUSION: Use of retrievable expandable nitinol stents seems to be a safe and effective method of treatment in selected patients with benign esophageal strictures.

Adult↗

Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus.

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance (R(N)), membrane time constant (tau(m)), and depolarizing "sag" in response to hyperpolarizing current pulses were similar in all subicular neurons, while R(N) and tau(m) were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.

Action Potentials↗