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Biomedical subjects

Y S Hong

Publications and source records attributed to Y S Hong.

At least 19 recordsLinked to original sources

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.

Aged↗

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 prescription of morphine for severe cancer pain by physicians in Korea.

BACKGROUND: This study was undertaken to identify predictors of the prescription of strong opioids, which are important for the management of severe cancer pain, by Korean physicians. METHODS: A questionnaire based on a hypothetical case designed to assess the prescription of morphine by physicians was administered to 800 specialists in the Korea Cancer Association, of whom 147 (18.4%) responded, and to 2200 specialists in the Korean Academy of Family Medicine, of whom 388 (17.6%) responded. We used a multidimensional approach to identify the predictors of prescription of morphine by physicians. RESULTS: In the hypothetical case scenario, only 16.5% of the respondents stated that they would prescribe morphine for severe cancer pain. Multiple logistic regression analysis showed that physicians with a positive attitude regarding opioid addiction [odds ratio (OR) 2.62; 95% confidence interval (CI) 1.54-4.46], experience of pain assessment (OR 2.09; 95% CI 1.13-3.87), recent residency training (OR 2.27; 95% CI 1.30-4.0) and positive self-evaluation as an oncology specialist (OR 2.60; 95% CI 1.41-4.78) were more likely to prescribe morphine. None of the 13 variables in the knowledge dimension significantly predicted prescription of morphine for severe cancer pain. CONCLUSIONS: The results of the survey suggest that we need to develop strategies to develop a positive attitude toward opioids, to increase experience in pain assessment and to improve cancer pain management training among Korean physicians.

Adult↗

Modulation of Anopheles gambiae gene expression in response to o'nyong-nyong virus infection.

To determine if gene expression of An. gambiae is modulated in response to o'nyong-nyong virus (ONNV) infection, we utilized cDNA microarrays including about 20 000 cDNAs. Gene expression levels of ONNV-infected female mosquitoes were compared to that of the uninfected control females harvested at 14 days postinfection. In response to ONNV infection, expression levels of 18 genes were significantly modulated, being at least two-fold up- or down-regulated. Quantitative real-time PCR analysis (qRT-PCR) further substantiated the differential expression of six of these genes in response to ONNV infection. These genes have similarity to a putative heat shock protein 70, DAN4, agglutinin attachment subunit, elongation factor 1 alpha and ribosomal protein L35. One gene, with sequence similarity to mitochondrial ribosomal protein L7, was down-regulated in infected mosquitoes. The expression levels and annotation of the differentially expressed genes are discussed in the context of host/virus interaction including host translation/replication factors, and intracellular transport pathways.

Animals↗

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer.

BACKGROUND: Capecitabine (Xeloda) is a novel, oral, selectively tumor-activated fluoropyrimidine with proven activity in the treatment of advanced colorectal cancer. This trial was conducted to evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients. PATIENTS AND METHODS: Forty-four patients received capecitabine 1250 mg/m2 twice daily (2500 mg/m2/day) for 14 days followed by 7 days of rest, for up to six cycles. RESULTS: Capecitabine produced an objective response rate of 34% (all partial responses) and stable disease in 14 patients (30%). The median time to disease progression (TTP) was 3.2 months [95% confidence interval (CI) 2.7-6.4 months] and median overall survival was 9.5 months (95% CI 6.9-13.2 months). Hand-foot syndrome (HFS), nausea, anorexia, diarrhea and vomiting were the most common adverse events. While HFS was the most frequent grade 3/4 toxicity (National Cancer Institute Common Toxicity Criteria), only 9% of patients experienced grade 3 HFS. Severe myelosuppression was not reported during the study. CONCLUSIONS: Capecitabine monotherapy is active and well tolerated as first-line therapy in patients with advanced/metastatic gastric cancer. Larger comparative trials investigating capecitabine-based combination regimens in patients with advanced gastric cancer are warranted.

Administration, Oral↗

Relationship between micropapillary component and micrometastasis in the regional lymph nodes of patients with stage I lung adenocarcinoma.

AIMS: To determine whether a micropapillary component is a prognostic predictor, with particular reference to nodal micrometastasis, in patients with stage I lung adenocarcinomas. METHODS AND RESULTS: Thirty-five cases with stage I lung adenocarcinomas, obtained from lobectomies or pneumonectomies, and 434 dissected hilar and mediastinal lymph nodes, were retrospectively reviewed. A micropapillary component and nodal micrometastasis were found in 16 (45.7%) and 14 (40%) of the 35 cases, respectively, with nodal micrometastasis in 24 (5.5%) of the 434 lymph nodes, in an immunohistochemical study using an anti-cytokeratin antibody. Ten (62.5%) of the 16 cases with a micropapillary component, and four (21.1%) of the remaining 19 cases, showed nodal micrometastases (P = 0.014). Kaplan-Meier survival curves demonstrated that there was no significant difference between the cases with and without a micropapillary component (P = 0.28). However, the 5 years' survival of the cases with and without nodal micrometastases were 71.4% and 35.7%, respectively (P = 0.03). CONCLUSIONS: A micropapillary component may be a manifestation of aggressive behaviour, as shown by frequent micrometastasis, for stage I lung adenocarcinomas.

Adenocarcinoma↗

Molecular evolutionary analysis of the widespread piggyBac transposon family and related "domesticated" sequences.

piggyBac is a short inverted-repeat-type DNA transposable element originally isolated from the genome of the moth Trichoplusia ni. It is currently the gene vector of choice for the transformation of various insect species. A few sequences with similarity to piggyBac have previously been identified from organisms such as humans ( Looper), the pufferfish Takifugu rubripes ( Pigibaku), Xenopus ( Tx), Daphnia ( Pokey), and the Oriental fruit fly Bactrocera dorsalis. We have now identified 50 piggyBac-like sequences from publicly available genome sequences and expressed sequence tags (ESTs). This survey allows the first comparative examination of the distinctive piggyBac transposase, suggesting that it might contain a highly divergent DDD domain, comparable to the widespread DDE domain found in many DNA transposases and retroviral integrases which consists of two absolutely conserved aspartic acids separated by about 70 amino acids with a highly conserved glutamic acid about 35 amino acids further away. Many piggyBac-like sequences were found in the genomes of a phylogenetically diverse range of organisms including fungi, plants, insects, crustaceans, urochordates, amphibians, fishes and mammals. Also, several instances of "domestication" of the piggyBac transposase sequence by the host genome for cellular functions were identified. Novel members of the piggyBac family may be useful in genetic engineering of many organisms.

Animals↗

Construction of a BAC library and generation of BAC end sequence-tagged connectors for genome sequencing of the African malaria mosquito Anopheles gambiae.

A Bacterial Artificial Chromosome (BAC) genomic DNA library of Anopheles gambiae, the major human malaria vector in sub-Saharan Africa, was constructed and characterized. This library (ND-TAM) is composed of 30,720 BAC clones in eighty 384-well plates. The estimated average insert size of the library is 133 kb, with an overall genome coverage of approximately 14-fold. The ends of approximately two-thirds of the clones in the library were sequenced, yielding 32,340 pair-mate ends. A statistical analysis (G-test) of the results of PCR screening of the library indicated a random distribution of BACs in the genome, although one gap encompassing the white locus on the X-chromosome was identified. Furthermore, combined with another previously constructed BAC library (ND-1), ~2,000 BACs have been physically mapped by polytene chromosomal in situ hybridization. These BAC end pair mates and physically mapped BACs have been useful for both the assembly of a fully sequenced A. gambiae genome and for linking the assembled sequence to the three polytene chromosomes. This ND-TAM library is now publicly available at both http://www.malaria.mr4.org/mr4pages/index.html/ and http://hbz.tamu.edu/, providing a valuable resource to the mosquito research community.

Animals↗

Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.

Dihydrolipoamide dehydrogenase (E3) deficiency with a clinical phenotype and genotype (Gly194Cys homozygous) previously identified only in Ashkenazi Jewish patients, was diagnosed in two Palestinian Arab siblings and two unrelated Ashkenazi Jewish patients. While three of the four patients died in childhood without specific treatment, the surviving patient at age 18 years may have benefited from long-term daily supplementation with a cocktail of riboflavin, biotin, coenzyme Q and carnitine.

Child↗

Quantification of proteinuria in children using the urinary protein-osmolality ratio.

A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m2/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061 +/- 0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073 +/- 0.014. Twenty-four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78 +/- 1.10 and Uprot/Uosm was 4.42 +/- 1.34. Twenty-four hour urinary protein excretion in group 2 was 1483.6 +/- 303.7 mg/m2/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r = 0.87, P < 0.001 and r = 0.88, P < 0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m2/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children.

Adolescent↗

Effects of human tissue plasminogen gene transfer on allograft coronary atherosclerosis.

BACKGROUND: Transplant coronary atherosclerosis is a major limiting factor to successful long-term cardiac transplantation. The depletion of tissue plasminogen activator (tPA) in the arteriolar smooth muscle cells has been associated with a higher incidence of accelerated graft atherosclerosis. In vivo overexpression of tPA may inhibit accelerated graft atherosclerosis and improve the long-term results of heart transplantation. We evaluated the feasibility, distribution, and effects of intracoronary transfer of the human tPA (htPA) gene in a rabbit heterotopic cardiac transplant model, using a novel cationic liposome compound designed for improved delivery to vascular endothelium. METHODS: Human tPA cDNA under the control of the SV40 promoter (100 microg) was complexed with the novel cationic liposome (+/-)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis(dodecyloxy)-1-propanaminium bromide (GAP: DLRIE) (50 microg), and delivered ex vivo to the donor heart by slow intracoronary infusion. Control hearts received an "empty" liposome preparation. Grafts were then implanted into recipient rabbits in the heterotopic cervical position. For the analysis of gene expression, beating donor hearts were collected at 4 days. To examine the effects of htPA expression on graft atherosclerosis, animals received a 0.5% cholesterol diet for 30 days posttransplant, as well as 10 mg/kg cyclosporine A daily. Beating hearts were collected at 30 days posttransplant and analyzed for the development of transplant atherosclerosis by image analysis. RESULTS: Northern blot analysis for the htPA messenger RNA (mRNA) transcripts showed significantly higher counts in hearts receiving the htPA gene as compared to controls. The distribution of these transcripts favored the left ventricle (LV) and septal regions over the right ventricle (RV). Scintillation analysis of specimens stained by immunoflourescence showed expression of htPA throughout the perivascular myocardium that was significantly higher in grafts transduced with the htPA gene than in control or native hearts. Expression in the vascular wall was also significantly enhanced. Scintillation counts per x 200 field were 262 +/- 145 in htPA-transduced hearts and 20 +/- 27 in controls (p = 0.001), and mean luminescence was 83.7 +/- 12.5 in htPA-transduced hearts and 62.9 +/- 12.8 in controls (p = 0.01). Intimal hyperplasia was assessed by mean percent luminal stenosis in small- and medium-sized arteries and was 31.12 +/- 23.5% in htPA-transduced hearts and 86.59 +/- 17.5% in control hearts (p < 0.0001). These results demonstrate that expression of the htPA gene can be induced by ex vivo intracoronary gene transfer at the time of allograft preservation. Liposome-mediated delivery of the htPA gene at the time of transplantation results in significant early transgene expression, and significantly inhibits the development of graft coronary atherosclerosis.

Animals↗

Antioxidant benzoylated flavan-3-ol glycoside from Celastrus orbiculatus.

A new flavan-3-ol glycoside, (-)-epicatechin-5-O-beta-D-glucosyl-3-benzoate (1), and two known compounds, (-)-epicatechin and (-)-epiafzelechin, were isolated from an EtOAc extract of Celastrus orbiculatus aerial parts that exhibited significant antioxidant effect in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay. The structure of 1 was elucidated by spectroscopic analyses, and compound 1 and its aglycon, (-)-epicatechin-3-benzoate (2), were found to be moderately active as antioxidants in the DPPH assay.

Antioxidants↗

Identification of HLA-A*11 variant (A*1107) in the Korean population.

We report here a new HLA-A*11 allele, A*1107, identified by sequencing based typing in the Korean population. The full-length sequencing of A*1107 was conducted on cDNA. HLA-A*1107 differs from HLA-A*1101 by a single nucleotide at position 399 of codon 109 in exon3 (TTC-->TTA), leading to an amino acid change from phenylalanine to leucine. But the serological profile of HLA-A*1107 did not exhibit the altered HLA-A11.

Alleles↗

Analysis of p53 and BAX mutations, loss of heterozygosity, p53 and BCL2 expression and apoptosis in basal cell carcinoma in Korean patients.

BACKGROUND: Apart from some Japanese studies, there are few data on the gene mutations involved in the development of basal cell carcinomas (BCC) in Koreans or other Asians. Objective To gain insight into the molecular pathogenesis of BCC in Koreans. METHODS: A collection of 33 cases of BCC were screened for mutations of p53 and BAX genes, p53 and BCL2 expression, loss of heterozygosity (LOH) and apoptosis. RESULTS: Mutations of p53, found in 9% (three of 33) of the cases, were all mis-sense mutations (G-->C transversions) at codon 246 on exon 7. In 6% (two of 33), BAX gene showed frameshift mutations resulting from deletions in the poly(G) tract. LOH on chromosome 9q was seen in 58% (14 of 24), and p53 mutations developed only among the 9q LOH+ cases; LOH on chromosome 18q, where BCL2 gene is located, was found in 13% (four of 30). Immunohistochemical expression of p53 was seen in 27% (nine of 33), and its expression did not coincide with p53 mutations. BCL2 expression was seen in 39% (13 of 33). Apoptosis was revealed in 21%. In BCC, 9q LOH and p53 mutations seem to be closely related; the immunoreactivity of p53 and its mutations were not directly related; and p53 and BCL2 expression were negatively correlated. Frameshift mutations of the BAX gene in BCC are documented for the first time. CONCLUSIONS: Various molecular mechanisms operate with redundant complexity in the pathogenesis of BCC. The LOH on chromosome 9q is the most frequent genetic alteration, as in other races; however, p53 mutations are much less frequent in Koreans than in Caucasians and suggest aetiologies other than ultraviolet radiation.

Adult↗

Left atrial appendage stenosis.

We describe an unusual case with an anatomic narrowing at the opening of the left atrial appendage demonstrated by two-dimensional color Doppler and continuous-wave Doppler transesophageal echocardiography.

Atrial Appendage↗

A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa B by targeting I kappa B phosphorylation.

A sesquiterpene lactone, costunolide (CTN), was identified from Magnolia grandiflora together with parthenolide (PTN) by its strong inhibition of LPS-induced NF-kappa B activation. CTN, which showed more potent inhibition than PTN in the NF-kappa B activation, strongly suppressed nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. RT-PCR and Western blot analyses demonstrated that CTN suppressed the expression of iNOS mRNA and protein in a dose-dependent manner. CTN also significantly inhibited LPS-induced DNA-binding activity of NF-kappa B as well as the LPS-induced degradation of I kappa B-alpha and -beta. Furthermore, CTN inhibited LPS-induced phosphorylation of I kappa B-alpha. These findings support that CTN inhibits NO production by down-regulating iNOS expression, at least, in part through the inhibition of I kappa Bs' phosphorylation and degradation, which are essential for the activation of NF-kappa B.

Animals↗