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Objective: We investigated how patients' spiritual and religious needs are addressed by healthcare staff in inpatient palliative care centers in Korea, a multi-religious country., Methods: We performed a cross-sectional, multicenter survey of terminal cancer patients in inpatient palliative care centers., Results: Approximately half (50.5%) of the patients reported that their spiritual and religious needs were addressed by healthcare staff. Patients whose needs were addressed reported better quality of life (QoL), as measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire for Palliative Care, than patients whose needs were not addressed (p<0.05), although these groups did not differ when measured using the Comprehensive QoL Scale. Patients with a religious affiliation [adjusted odds ratio (aOR), 2.38; 95% confidence interval (CI), 0.70-8.05], those who were admitted to a religious palliative care center (aOR, 2.61; 95% CI, 0.86-7.96), and those whose religious affiliation was the same as that of the palliative care center (aOR, 2.42; 95% CI, 0.96-6.07) tended to have their spiritual and religious needs addressed, although not statistically significant., Conclusions: Although patients whose spiritual and religious needs were addressed by healthcare staff showed significantly better QoL, such needs were not addressed in a significant proportion of patients, especially those who were not religious or were admitted to non-religious palliative care centers. Strategies should be developed to ensure that spiritual care is provided to all patients with terminal cancer, regardless of the religious background of the patient., (Copyright © 2011 John Wiley & Sons, Ltd.)

Endosulfan is an organochlorine insecticide and has been implicated in neurotoxicity, hepatotoxicity, immunosuppression and teratogenicity. However, the molecular mechanism of endosulfan toxicity is not yet clear. Recent studies demonstrated that oxidative stress induced by endosulfan is involved in its toxicity and accumulating evidence suggests that endosulfan can modulate the activities of stress-responsive signal transduction pathways including extracellular signal regulated kinases (ERK) 1/2. However, none of the previous studies investigated the ability of endosulfan to modulate activating protein-1 (AP-1) binding and antioxidant response element (ARE)-mediated transcription as an underlying mechanism of endosulfan toxicity. In this report, we show that treatment of HepG2 cells with endosulfan significantly increased oxidative stress-responsive transcription via AP-1 activation. In addition, endosulfan-induced transcription was enhanced in cells depleted of glutathione by buthionine sulfoximine (BSO) treatment. Exposure to endosulfan resulted in a significant increase in the activities of MAPKs, ERK1/2 and p38. Endosulfan-induced increases in enzymatic activities of these MAPKs were consistent with MAPK phosphorylation. Endosulfan exposure also caused an increase in c-Jun phosphorylation. These results suggest a model for endosulfan toxicity in which endosulfan increases ERK1/2 and p38 activities and these activated MAPKs then increase c-Jun phosphorylation. Phosphorylated c-Jun, in turn, increases AP-1 activity, which results in activation of ARE-mediated transcription., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Previous global transcriptome and interactome analyses of copper-treated HepG2 cells identified hepatocyte nuclear factor 4α (HNF4α) as a potential master regulator of copper-responsive transcription. Copper exposure caused a decrease in the expression of HNF4α at both mRNA and protein levels, which was accompanied by a decrease in the level of HNF4α binding to its consensus DNA binding sequence. qRT-PCR and RNAi studies demonstrated that changes in HNF4α expression ultimately affected the expressions of its down-stream target genes. Analysis of upstream regulators of HNF4α expression, including p53 and ATF3, showed that copper caused an increase in the steady-state levels of these proteins. These results support a model for copper-responsive transcription in which the metal affects ATF3 expression and stabilizes p53 resulting in the down-regulation of HNF4α expression. In addition, copper may directly affect p53 protein levels. The suppression of HNF4α activity may contribute to the molecular mechanisms underlying the physiological and toxicological consequences of copper toxicity in hepatic-derived cells., (Published by Elsevier B.V.)

Copper is a persistent environmental contaminant, and exposure to elevated levels of this transition metal can result in a variety of pathologies. Copper affects the transcription of multiple defense and repair genes to protect against metal-induced pathologies. HepG2 cells were treated with copper under multiple conditions and microarray analyses were previously performed to better understand the mechanisms by which copper affects the transcription of stress-responsive genes. Analysis of the microarray data indicated that copper modulates multiple signal transduction pathways, including those mediated by NF-kappaB. Luciferase assays, quantitative reverse transcription real-time PCR, and chemical inhibition in HepG2 cells validated the microarray results and confirmed that NF-kappaB was activated by stress-inducible concentrations of copper. In addition, two novel NF-kappaB-regulated genes, SRXN1 (sulfiredoxin 1 homolog) and ZFAND2A (zinc-finger, AN1-type domain 2A), were identified. Our results indicate that the activation of NF-kappaB may be important for survival under elevated concentrations of copper.

Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 microM copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis, morphogenesis, and negative regulation of biomolecule metabolism. The global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. This analysis indicated that copper modulates signal transduction pathways associated with MAPK, NF-kappaB, death receptor, IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement and coagulation, and sonic hedgehog signaling. These results provide insights into the global and molecular mechanisms regulating the physiological and toxicological responses to metal exposure.

An epidemiologic study was performed to determine the genetic variability of rotaviruses in Seoul, South Korea. In 3,174 stool specimens from children with acute diarrhea at five referral hospitals, 571 (18%) possessed the antigen of group A rotavirus detectable by ELISA--10.8% in 2004 and 28.1% in 2005. VP7 genotyping revealed that the G3 type was found in 25.6% of all typed isolates, G4 in 23.8%, G2 in 21.6%, and G1 in 17.6%. VP4 genotyping showed that the P[8] type was detected in 66.7%, P[6] in 15.6%, P[4] in 13.0%, and P[9] in 0.2%. Because the variant P[8] type could not be amplified initially by conventional P typing primers (1T-1), PCR were performed using newly designed 1T-1S primer, which revealed that 307 specimens were the variant P[8] type. Uncommon combinations such as G4P[6] and G2P[8] were also found with relatively high prevalence, 14.6% and 12.8%, respectively. Variant P[8] types were associated with an outbreak of rotavirus in 2005.

The idea that human bocavirus (hBoV) infection possibly plays a role in gastroenteritis has been suggested because of the frequent manifestation of gastrointestinal symptoms. The purpose of this study was to investigate the prevalence of hBoV in children with gastroenteritis. We studied the etiologic agents in 962 children hospitalized with gastroenteritis. Viral etiologic agents were detected by enzyme-linked immunosorbent assay or reverse-transcriptase polymerase chain reaction. A viral agent was found in 44.4% of the study population: rotavirus, norovirus, adenovirus, and astrovirus were detected in 25.7%, 13.7%, 3.0%, and 1.1% of the study population, respectively; hBoV was detected in 0.8%, which suggests that it might play a minor role in gastroenteritis.

The hypothesis that copper modulates the activity of intracellular signal transduction pathways to affect transcription, which ultimately disrupts normal development was investigated. Preliminary analysis of transcriptomes from HepG2 cells exposed to copper for 4 and 24 h identified 19 and 7 up-regulated genes (twofold; p

Polychlorinated biphenyls (PCBs) are persistent organic pollutants. Exposure to PCB126 (3,3',4,4',5-pentachlorobiphenyl), a non-ortho-chlorinated, coplanar congener has been correlated with the production of reactive oxygen species in vivo. In this report, we show that treatment of HepG2 cells with PCB126 significantly increases oxidative-stress-responsive transcription. In addition, PCB126-induced transcription is enhanced in cells depleted of glutathione. Exposure to PCB126 induces a cellular stress response in HepG2 cells that results in a significant increase in the activity of the mitogen activated protein kinases: extracellular signal regulated kinases 1/2 and p38. PCB126 exposure also causes an increase in c-Jun phosphorylation. These results suggest a model for PCB126 toxicity in which PCB126 exposure induces oxidative stress that causes an increase in mitogen-activated protein kinase (MAPK) activities and a subsequent increase in c-Jun phosphorylation. Activation of c-Jun results in enhanced activating protein-1 (AP-1) activity, which leads to elevated expression of antioxidant responsive element (ARE)/AP-1-dependent genes.

Six Caenorhabditis elegans genes that are homologous to the novel, cadmium-responsive gene cdr-1 have been identified and characterized. Nucleotide and amino acid sequence comparisons among the CDR family, which includes cdr-1, cdr-2, cdr-3, cdr-4, cdr-5, cdr-6, and cdr-7, reveals a high degree of identity among the seven members in this family. There are high levels of amino acid and nucleotide sequence similarity in the lengths of the open reading frames, predicted sizes, and protein characteristics. The seven proteins are predicted to be extremely hydrophobic, and are classified as integral membrane proteins. Structural analysis of the predicted proteins suggests that they may have similar biological functions. In response to cadmium exposure, cdr-1, cdr-2, cdr-3, and cdr-4 transcription significantly increases. In contrast, the levels of cdr-5, cdr-6, and cdr-7 transcription are not significantly affected or inhibited by cadmium exposure. Further, in non-exposed C. elegans, cdr-2, cdr-4, cdr-6, and cdr-7 are constitutively expressed. When CDR-1 expression was inhibited using RNAi, numerous fluid droplets were observed throughout the nematode body cavity. This phenotype became more pronounced in the presence of hypotonic stress. This suggests that CDR-1 may function in osmoregulation to maintain salt balance in C. elegans.

As a formal recommendation from an Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) workshop review of the Frog Embryo Teratogenesis Assay--Xenopus (FETAX) developmental toxicity model, the use of Xenopus tropicalis as an alternative test species for this model was evaluated. Three test substances with varying developmental toxicity potentials were evaluated using FETAX modified to accommodate the use of X. tropicalis. Two separate definitive concentration-response tests were performed with isoniazid, methotrexate, and 6-aminonicotinamide. Historical FETAX results with X. laevis were compared to the results from FETAX assays with X. tropicalis. Test with X. tropicalis indicated that each of the compounds possessed teratogenic potential with varying degrees of potency: 6-aminonicotinamide > methotrexate > isoniazid. Based on overt teratogenicity, but not embryo-lethality, results from these studies indicated that these two species responded similarly to the test compounds. Malformation syndromes induced in both species were similar in X. tropicalis and X. laevis. These results suggested that X. tropicalis should be further evaluated as an alternative test organism for the FETAX model.

Three hundred forty-eight fecal specimens collected from young children with acute diarrhea in Seoul, Korea between January 1998 and February 2000 were examined for G and P types. Of these, 205 samples (59%) were confirmed as group A rotavirus by ELISA for the detection of VP6 antigen. Confirmed rotavirus isolates were characterized using G serotyping ELISA and RT-PCR methodologies for G and P genotyping of the outer capsid proteins VP7 and VP4, respectively. Serotyping of the outer capsid protein, VP7, revealed G4 as the dominant circulating serotype (41%) followed by G1 (28%) and quite a high incidence of mixed infection (14%). Genotyping of the VP4 protein was carried out on 55 of the rotavirus isolates with the dominant type being P[8] (46%). Of interest were a number of unusual G and P type combinations detected in Korea for the first time, especially the P[4] genotype associated with non-G2 serotypes. There were also a number of P[6] isolates identified including one G2P[6] isolate., (Copyright 2003 Wiley-Liss, Inc.)

16S rDNA sequence analysis and repetitive element sequence-based PCR (rep-PCR) genomic fingerprinting were evaluated on 11 type strains of the genus Yersinia and 17 recognized serotype strains of Y. pseudotuberculosis to investigate their genetic relatedness and to establish the value of techniques for the identification of Y. pseudotuberculosis. A phylogenetic tree constructed from 16S rDNA sequences showed that the type strains of Yersinia species formed distinct clusters with the exception of Y. pestis and Y. pseudotuberculosis. Moreover, Y. pestis NCTC 5923T was found to be closely related to Y. pseudotuberculosis serotypes 1b, 3, and 7. Dendrograms generated from REP-PCR, and ERIC-PCR data revealed that members of the genus Yersinia differed from each other with the degree of similarity 62% and 58%, respectively. However, the BOX-PCR results showed that Y. pestis 5923T clustered with the Y. pseudotuberculosis group with a degree of similarity 74%. According to these findings, 16S rDNA sequence analysis was unable to reliably discriminate Y. pseudotuberculosis from Y. pestis. However, REP-PCR and especially ERIC-PCR provided an effective means of differentiating between members of the taxa.