Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 19 recordsLinked to original sources

PubMed2006

Selective surgery and adjuvant therapy based on risk classifications of well-differentiated thyroid cancer.

BACKGROUND: The prognosis of well-differentiated thyroid cancer has been stratified into low- and high-risk groups. These risk groups can be used to predict prognosis and to guide treatment. METHODS: Retrospective study of 962 patients with well-differentiated thyroid cancer treated from 1940 to 1998. Stratification into low- and high-risk groups based on age, metastases, extent, and size (AMES). Effects on survival of surgery, lymph node dissection, and radiation therapy were examined. RESULTS: Seven hundred twenty-eight cases were papillary and 234 were follicular carcinoma. Seven hundred-fifty cases were low risk and 207 high risk. Twenty-year survival was 97.4% in the low-risk patients and 54.0% in high-risk patients (P < 0.001); it was 63.2% in the younger high-risk group and 41.0% in the older high-risk group (P < 0.001). Older high-risk patients had a survival advantage with bilateral thyroidectomy. Extent of surgery did not change survival in either the younger high-risk group or the low-risk group. Lymph node dissection and radioactive iodine ablation did not have an impact on survival. DISCUSSION: Well-differentiated thyroid cancer in low-risk patients has a favorable outcome regardless of treatment. Low-risk patients can be safely treated with unilateral thyroidectomy alone. Risk stratification with a modification of the AMES criteria can be used to guide treatment.

Adenocarcinoma, Follicular↗

PubMed2006

Early growth response transcription factor EGR-1 regulates Galphaq gene in megakaryocytic cells.

BACKGROUND: Galphaq (Gene GNAQ) plays a major role in platelet signal transduction but little is known regarding its transcriptional regulation. OBJECTIVES: We studied Galphaq promoter activity using luciferase reporter gene assays in human erythroleukemia (HEL) cells treated with phorbol 12-myristate 13-acetate (PMA) for 24 h to induce megakaryocytic transformation. METHODS AND RESULTS: PMA-treated HEL cells showed enhanced Galphaq expression. Reporter (luciferase) gene studies on 5' upstream construct (up to -116 bp from ATG) revealed a negative regulatory site at -238/-202 and two positive sites at -203/-138 and -1116/-731. The positive regulatory region -203/-138 contained overlapping Sp1/AP-2/EGR-1 consensus sites. Gel shift studies on Galphaq oligonucleotides 1 (-203/-175) and 2 (-174/-152) using HEL cell extracts demonstrated protein binding that was due to early growth response factor EGR-1 at two sites. Mutations in either EGR-1 site markedly decreased the gene activity, indicating functional relevance. Mutation of consensus E-Box motif (-185/-180) had no effect. Reduction in the expression of endogenous EGR-1 with antisense oligonucleotide to EGR-1 inhibited PMA-induced Galphaq transcription. Correspondingly, Egr-1 deficient mouse platelets also showed approximately 50% reduction in the Galphaq expression relative to wild-type platelets. CONCLUSIONS: These studies suggest that Galphaq gene is regulated during PMA-induced megakaryocytic differentiation by EGR-1, an early growth response transcription factor that regulates a wide array of genes and plays a major role in diverse activities, including cell proliferation, differentiation and apoptosis, and in vascular response to injury and atherosclerosis.

Animals↗

PubMed2006

Human papillomavirus type 16 E6 protein interacts with cystic fibrosis transmembrane regulator-associated ligand and promotes E6-associated protein-mediated ubiquitination and proteasomal degradation.

The PDZ proteins such as hDLG, hScrib and MAGIs function as the membrane-associated protein scaffolds and have been shown to interact with the high-risk human papillomavirus (HPV) E6s. In this report, we identify a Golgi-associated PDZ protein, cystic fibrosis transmembrane regulator-associated ligand (CAL) as a cellular target of HPV16 E6 by the proteomic approach. The carboxy-terminal PDZ-binding motif of HPV16 E6 specifically interacts with the PDZ domain of CAL, and the interaction enhances proteasome-mediated degradation of CAL. HPV16 E6 interacts with CAL more strongly and degrades it better than HPV18 E6 owing to the more compatible PDZ-binding motif. CAL is ubiquitinated by the E6/E6-associated protein (E6AP) complex or by E6AP alone, albeit less efficiently, which indicates that it could be a normal target of E6AP. Although it downregulates CAL at the transcript level, small interfering RNA-induced depletion of HPV16 E6 in Caski cells stabilizes CAL at the protein level, suggesting that HPV16 E6 mediates the proteasomal degradation of CAL in HPV-positive cervical cancer cells. HPV16 E6 may tightly regulate the vesicular trafficking processes by interacting with CAL, and such a modification can contribute to the development of cervical cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Gene expression signatures associated with the resistance to imatinib.

Imatinib (imatinib mesylate, STI-571, Gleevec) is a selective BCR-ABL tyrosine kinase inhibitor that has been used as a highly effective chemoagent for treating chronic myelogenous leukemia. However, the initial response to imatinib is often followed by the recurrence of a resistant form of the disease, which is major obstacle to many therapeutic modalities. The aim of this study was to identify the gene expression signatures that confer resistance to imatinib. A series of four resistant K562 sublines was established with different imatinib dosage (200, 400, 600 and 800 nM) and analyzed using microarray technology. The transcripts of the genes showing universal or dose-dependent expression changes across the resistant sublines were identified. The gene sets associated with the imatinib-resistance were also identified using gene set enrichment analysis. In the resistant K562 sublines, the transcription- and apoptosis-related expression signatures were upregulated, whereas those related to the protein and energy metabolism were downregulated. Several genes identified in this study such as IGF1 and RAB11A have the potential to become surrogate markers useful in a clinical evaluation of imatinib-resistant patients without BCR-ABL mutation. The expression signatures identified in this study provide insights into the mechanism of imatinib-resistance and are expected to facilitate the development of an effective diagnostic and therapeutic strategy.

Antineoplastic Agents↗

PubMed2006

Protective effects of Glycyrrhiza uralensis Fisch. on the cognitive deficits caused by beta-amyloid peptide 25-35 in young mice.

Amyloid beta protein (Abeta) may be involved in the progression of Alzheimer's disease (AD), by acting as a neurotoxin and eliciting oxidative stress. This study was designed to determine the effects of Glycyrrhiza uralensis Fisch. water extract (GWE) on the cognitive deficits and oxidative stress induced by the administration of Abeta(25-35) in mice. Mice in two of the four animal groups were fed an experimental diet containing either 0.5 or 1% GWE for the entire 6-week experimental period. Control mice and a further experimental group were fed a non-GWE diet. Abeta(25-35) was administered to the three experimental groups by intracerebroventricular (i.c.v.) injection (10 microg/10 microl/mouse) once per week in weeks 5 and 6 of the experimental period. Behavioral changes were assessed using both a passive avoidance (after the injection of Abeta(25-35) in week 5) and the Morris water-maze tests (after the injection of Abeta(25-35) in week 6). Control animals were administered vehicle alone. The prolonged consumption of a diet containing GWE ameliorated the cognitive deficits caused by the i.c.v. injections of Abeta(25-35). Treatment with Abeta(25-35) led to higher concentrations of thiobarbituric acid reactive substances in the brain, and GWE attenuated this response. There was a decrease in catalase activity in the group provided with 1% GWE. Acetylcholinesterase activity was significantly reduced in the brains of all GWE-treated animals compared to that in the non-GWE-fed experimental group. These results suggest that GWE exerts a protective effect against the cognitive impairments often observed in AD, and that in mice this effect is mediated by antioxidant actions against oxidative stress.

Aging↗

PubMed2006

Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression.

Amyloid precursor protein (APP) is a member of a gene family that includes two APP-like proteins, APLP1 and 2. Recently, it has been reported that APLP1 and 2 undergo presenilin-dependent gamma-secretase cleavage, as does APP, resulting in the release of an approximately 6 kDa intracellular C-terminal domain (ICD), which can translocate into the nucleus. In this study, we demonstrate that the APLP2-ICDs interact with CP2/LSF/LBP1 (CP2) transcription factor in the nucleus and induce the expression of glycogen synthase kinase 3beta (GSK-3beta), which has broad-ranged substrates such as tau- and beta-catenin. The significance of this finding is substantiated by the in vivo evidence of the increase in the immunoreactivities for the nuclear C-terminal fragments of APLP2, and for GSK-3beta in the AD patients' brain. Taken together, these results suggest that APLP2-ICDs contribute to the AD pathogenesis, by inducing GSK-3beta expression through the interaction with CP2 transcription factor in the nucleus.

Active Transport, Cell Nucleus↗

PubMed2006

Promoter methylation of helicase-like transcription factor is associated with the early stages of gastric cancer with family history.

BACKGROUND: To investigate the clinicopathological significance of promoter methylation of the helicase-like transcription factor (HLTF) in primary gastric cancer. PATIENTS AND METHODS: Two-hundred fifty six patients participated in this study. Methylation status of HLTF gene was evaluated in fresh-frozen tissues by the methylation-specific polymerase chain reaction. All statistical analyses were two-sided, with a 5% type I error rate. RESULTS: Aberrant methylation of HLTF was found in 98 (38%) of 256 gastric cancer patients. HLTF methylation was significantly associated with a family history in the early stages of gastric cancer, regardless of histologic types. In intestinal-type cases, HLTF methylation occurred in 15 (56%) of 27 patients with family histories, and in 26 (31%) of 85 patients without family histories (P = 0.02). In diffuse-type cases, patients with family histories were also found to exhibit a higher prevalence of HLTF methylation than those without family histories (61% vs. 34%; P = 0.009). HLTF methylation in both of the histologic types occurred in about 70-90% of the early stage cases in which the patient had a family history and in 15-30% of cases in which the patient did not have a family history. In our multivariate logistic regression analysis, the stage 1-2 cases with family histories were determined to carry a higher risk of HLTF methylation than did the stage 3-4 cases without family histories in both the intestinal-type (OR = 6.01, 95% CI = 1.20-30.01, P = 0.02) and the diffuse-type cancers (OR = 8.25, 95% CI = 1.67-40.86, P = 0.009). CONCLUSIONS: These results suggest that HLTF methylation may play a crucial role in the early stages of gastric carcinogenesis in patients with family histories and may be a valuable susceptible marker for the risk of gastric cancer in individuals with family histories.

Aged↗

PubMed2006

Clipping vs coiling of posterior communicating artery aneurysms with third nerve palsy.

The authors investigated the evolution of third nerve palsy in patients with posterior communicating artery aneurysms who underwent coiling vs clipping. There was no statistical difference of complete third nerve palsy recovery in both treatments. Both techniques were of clinical benefit. Older age, diabetes, delayed interventions, and complete third nerve palsy at presentation indicated a poor prognosis for recovery.

Adult↗

PubMed2006

Intrathecal implants of microencapsulated xenogenic chromaffin cells provide a long-term source of analgesic substances.

Adrenal medullary chromaffin cells secrete several neuroactive substances including catecholamines and opioid peptides that produce analgesic effects in the central nervous system. This study was designed to investigate whether intrathecal microencapsulated chromaffin cells could release analgesic materials producing antiallodynic effects on the chronic neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Prior to intrathecal implantation, chromaffin cells were encapsulated with alginate and poly-L-lysine to protect them from the host immune system. Behavior tests were performed before CCI, 1 week later, and at 4, 7, 14, 21, 28 days postimplantation. At the end of study, we performed cerebrospinal fluid (CSF) collection and implant retrieval. We observed that intrathecal implantation of encapsulated xenogenic chromaffin cells reduced the mechanical and cold allodynia in a model of neuropathic pain. CSF levels of catecholamines and metenkephalin in the rats that received implants were higher than the controls. In addition, we observed chronic survival of implants. These results suggested that intrathecal microencapsulated chromaffin cells may represent a new approach to chronic neuropathic pain management.

Absorbable Implants↗

PubMed2006

Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma.

To understand the prognostic value of lymphocyte recovery after autologous peripheral blood stem cell transplantation (APBSCT), we performed a retrospective study of 59 newly diagnosed multiple myeloma (MM) patients who underwent frontline APBSCT. Conditioning regimens were melphalan 100 mg/m(2) for 2 days. Following APBSCT, all patients showed complete or partial response. Median follow-up time was 29.57 months and median recovery of absolute lymphocyte count (ALC) > or =1000/mm(3) was 23 days. Univariate analysis revealed that significant predictors of overall survival (OS) included bone marrow (BM) plasma cells < or =40% at diagnosis (P=0.0243) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0156). Positive predictors for progression-free survival (PFS) were BM plasma cells < or =40% at diagnosis (P=0.0134) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0243). Absolute neutrophil count > or =1000/mm(3) on day +12 was marginally significant for OS and PFS (P=0.0821 and P=0.1153, respectively). Multivariate analysis showed that ALC > or =1000/mm(3) on day +23 independently predicted OS (P=0.031) and prolonged PFS (P=0.011), and that serum beta2-microglobulin was marginally significant for prolonged OS (P=0.066). In conclusion, ALC recovery was an independent predictor of both OS and PFS in MM.

Adult↗

PubMed2006

Dysplastic naevi with moderate to severe histological dysplasia: a risk factor for melanoma.

BACKGROUND: The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma. OBJECTIVES: To estimate the risk of melanoma associated with HDN. Secondarily, the risk associated with number of naevi and large naevi is estimated. METHODS: We enrolled 80 patients with newly diagnosed melanoma along with 80 spousal controls. After obtaining information on melanoma risk factors and performing a complete cutaneous examination, the most clinically atypical naevus was biopsied in both cases and controls. Histological dysplasia was then assessed independently by 13 dermatopathologists (0, no dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The dermatopathologists were blinded as to whether the naevi were from melanoma subjects or controls. Multivariate analyses were performed to determine if there was an independent association between the degree of histological dysplasia in naevi and a personal history of melanoma. RESULTS: In persons with naevi receiving an average score of > 1 (i.e. naevi considered to have greater than mild histological dysplasia), there was an increased risk of melanoma [odds ratio (OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few dermatopathologists reliably graded naevi of subjects with melanoma as being more dysplastic than naevi of control subjects. Among the entire group, the interobserver reliability associated with grading histological dysplasia in naevi was poor (weighted kappa 0.28). CONCLUSIONS: HDN do appear to confer an independent risk of melanoma. However, this result may add more to our biological understanding of melanoma risk than to clinical assessment of risk, because HDN assessed by a single pathologist generally cannot be used to assess risk of melanoma. Future studies should be directed at establishing reproducible, predictive criteria for grading naevi.

Adult↗

PubMed2006

Fentanyl reduces desflurane-induced airway irritability following thiopental administration in children.

BACKGROUND: Airway irritation is a major drawback of desflurane anesthesia. This study was designed to evaluate the effect of intravenous fentanyl given before thiopental induction on airway irritation caused by a stepwise increase in desflurane in children. METHODS: Eighty children (2-8 years) were enrolled in a randomized, double-blind study. Forty received saline and 40 received 2 microg/kg of fentanyl intravenously; this was followed by thiopental sodium 5 mg/kg in both groups. Patients were assistant-ventilated with desflurane 1%, which was then increased by 1% every six breaths up to 10%. During this period, cough, secretion, excitation and apnea were graded and the desflurane concentration at which airway irritation symptoms first occurred was recorded. The results were analyzed using Pearson's chi-squared test. RESULTS: The incidence of typical airway irritation events was lower with fentanyl than with saline (cough, 2.5% vs. 42.5%; secretion, 27.5% vs. 82.5%; excitation, 10% vs. 82.5%; apnea, 20% vs. 65%; P < 0.05). The mean expired desflurane concentration at which the first airway irritation symptom occurred was greater with fentanyl than with saline (7.3% vs. 5.5%, P < 0.05). CONCLUSIONS: Intravenous fentanyl in children reduces airway complications caused by desflurane.

Analgesics, Opioid↗

PubMed2006

Measuring the full economic costs of diet, physical activity and obesity-related chronic diseases.

Most studies that have focused on the costs of obesity have ignored the direct effects of obesity-related patterns of diet and physical activity. This study reviews the full effects of each component--poor dietary and physical activity patterns and obesity--on morbidity, mortality and productivity. The direct healthcare costs are based on a review of the effects of these factors on key diseases and the related medical care costs of each disease. The indirect costs on reduced disability, mortality and sickness during the period of active labour force participation prior to retirement are also examined. A case study is prepared for China to provide some guidance in the utilization of this review for economic analysis of obesity. The case study shows that the indirect costs are often far more important than the direct medical care costs. The Chinese case study found that the indirect effects of obesity and obesity-related dietary and physical activity patterns range between 3.58% and 8.73% of gross national product (GNP) in 2000 and 2025 respectively.

Absenteeism↗

PubMed2006

Differentiation of outer membrane proteins from Salmonellaenterica serotypes using Fourier transform infrared spectroscopy and chemometrics.

AIMS: To differentiate between outer membrane proteins (OMPs) from six Salmonellaenterica serotypes using a Fourier transform infrared (FTIR) spectroscopy method and chemometrics. METHODS AND RESULTS: The OMPs from Salmonella serotypes (Typhimurium, Enteritidis, Thomasville, Hadar, Seftenberg and Brandenburg) were isolated using a sarcosyl extraction method. OMP profiles on SDS-PAGE exhibited two or three bands between 48 and 54 kDa. Spectra of 10 microl of OMP preparations (5 mg ml(-1)) dried on a gold reflective slide were collected using 128 scans at 4 cm(-1) resolution and units of log (1/R) and analyzed using canonical variate analysis (CVA) and linear discriminant analysis (LDA). The CVA of Salmonella OMP spectra in the 1800-1500 cm(-1) region separated the serotypes and LDA provided a 100% correct classification. CONCLUSIONS: The use of a FTIR method combined with chemometrics provided better differentiation of Salmonella OMPs than the OMP pattern analysis by SDS-PAGE. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to demonstrate that spectra of OMP extracts from Salmonella serotypes can be used for 100% correct classification of the serotypes studied.

Bacterial Outer Membrane Proteins↗

PubMed2006

P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation.

BACKGROUND: Thromboxane A2 (TXA2) is a positive feedback lipid mediator that is generated upon stimulation of platelets with various agonists. Aspirin works as an antithrombotic drug by blocking the generation of TXA2. The aim of this study was to evaluate the role of the purinergic P2Y receptors in thrombin-induced TXA2 generation. RESULTS: PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin, induced the activation of cytosolic phospholipase A2 (cPLA2), release of arachidonic acid (AA) from membrane-bound phospholipids, and subsequent TXA2 generation in human platelets. The actions of these agonists were significantly inhibited in the presence of the P2Y12 receptor antagonist, AR-C69931MX, but not the P2Y1 receptor antagonist, MRS2179. In addition, AYPGKF- and thrombin-induced TXA2 generation was significantly reduced in platelets from mice dosed with clopidogrel, confirming the results obtained with the human platelets. Also, Pearl mouse platelets that lack releasable nucleotides generated significantly less TXA2 when compared with the wild-type littermates in response to PAR stimulation. Inhibition of extracellular signal-regulated protein kinase 1/2 (Erk 1/2) activation using U0126, an inhibitor of MAP kinase kinase (MEK), suppressed PAR-mediated cPLA2 phosphorylation and TXA2 generation. Further, platelets that were pretreated with AR-C69931MX, as well as Pearl mouse platelets, displayed the reduced levels of Erk1/2 phosphorylation upon stimulation with the PAR agonists. CONCLUSIONS: Based on these findings, we conclude that thrombin-induced Erk1/2 activation is essential for PAR-mediated TXA2 generation, which is potentiated by the P2Y12 receptor-mediated signaling pathway but not the P2Y1 receptor-mediated signaling pathway. Finally, using selective inhibitors of Src kinases, we show that PAR-mediated Src activation precedes Erk1/2 activation.

Adenosine Monophosphate↗

PubMed2006

Rule-based fuzzy inference system for estimating the influent COD/N ratio and ammonia load to a sequencing batch reactor.

A fuzzy inference system using sensor measurements was developed to estimate the influent COD/N ratio and ammonia load. The sensors measured ORP, DO and pH. The sensor profiles had a close relationship with the influent COD/N ratio and ammonia load. To confirm this operational knowledge for constructing a rule set, a correlation analysis was conducted. The results showed that a rule generation method based only on operational knowledge did not generate a sufficiently accurate relationship between sensor measurements and target variables. To compensate for this defect, a decision tree algorithm was used as a standardized method for rule generation. Given a set of inputs, this algorithm was used to determine the output variables. However, the generated rules could not estimate the continuous influent COD/N ratio and ammonia load. Fuzzified rules and the fuzzy inference system were developed to overcome this problem. The fuzzy inference system estimated the influent COD/N ratio and ammonia load quite well. When these results were compared to the results from a predictive polynomial neural network model, the fuzzy inference system was more stable.

Algorithms↗

PubMed2006

Knowledge-based control and case-based diagnosis based upon empirical knowledge and fuzzy logic for the SBR plant.

Because biological wastewater treatment plants (WWTPs) involve a long time-delay and various disturbances, in general, skilled operators manually control the plant based on empirical knowledge. And operators usually diagnose the plant using similar cases experienced in the past. For the effective management of the plant, system automation has to be accomplished based upon operating recipes. This paper introduces automatic control and diagnosis based upon the operator's knowledge. Fuzzy logic was employed to design this knowledge-based controller because fuzzy logic can convert the linguistic information to rules. The controller can manage the influent and external carbon in considering the loading rate. The input of the controller is not the loading rate but the dissolved oxygen (DO) lag-time, which has a strong relation to the loading rate. This approach can replace an expensive sensor, which measures the loading rate and ammonia concentration in the reactor, with a cheaper DO sensor. The proposed controller can assure optimal operation and prevent the over-feeding problem. Case-based diagnosis was achieved by the analysis of profile patterns collected from the past. A new test profile was diagnosed by comparing it with template patterns containing normal and abnormal cases. The proposed control and diagnostic system will guarantee the effective and stable operation of WWTPs.

Ammonia↗

PubMed2006

Distribution of dioxins in surface soils and river-mouth sediments and their relevance to watershed properties.

The dioxins toxic equivalent (TEQ) concentration in surface soils, river sediments and river-mouth sediments was measured by the CALUX assay in the Yasu and Ado River basins around Lake Biwa, Japan. In order to examine the distribution of dioxins in each watershed, we evaluated and compared the correlation between the dioxins TEQ concentration and the solid characteristics (i.e. organic carbon content and particle size distribution) of all samples. In both basins, the dioxins TEQ concentration in forest soil correspondingly showed a very good linear relationship to organic carbon content. On the other hand, the dioxins TEQ concentration in paddy field was significantly high, although organic carbon content was relatively low. Generally, the smaller particles have the higher dioxins TEQ concentrations in surface soils, and river sediments were composed of very coarse particles and had relatively low dioxins TEQ concentration. Therefore, we expected high dioxins TEQ concentration in river-mouth sediment, which was, however, not the case. Although the dioxins TEQ concentration in river-mouth sediments is low, the degree of dioxins pollution was different in each basin. The difference was considered to come from the difference of watershed properties including land use, river-slope, dam construction as well as the surface soil pollution.

Carbon↗