Search PubMed⌕ Search

Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 271 records · Page 15Linked to original sources
PubMed2001

Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production.

The Akt/protein kinase B (PKB) serine/threonine kinase is well known as an important mediator of many cell survival signaling pathways. Here, we demonstrate for the first time a major role of Akt/PKB in the cell invasion properties of the highly metastatic cell line HT1080. Using confocal microscopic analyses of live samples, we found Akt/PKB to be localized in the leading edge membrane area of migrating HT1080 cells. This localization was dependent on phosphoinositide 3-kinase and required the lipid binding ability of the phosphoinositide binding pleckstrin homology domain of Akt/PKB. We examined the possible function of Akt/PKB in HT1080 invasion. Surprisingly, Akt/PKB potently promoted HT1080 invasion, by increasing cell motility and matrix metalloproteinase-9 (MMP-9) production, in a manner highly dependent on its kinase activity and membrane-translocating ability. The increase in MMP-9 production was mediated by activation of nuclear factor-kappaB transcriptional activity by Akt/PKB. However, Akt/PKB did not affect the cell-cell or cell-matrix adhesion properties of HT1080. Our findings thus establish Akt/PKB as a major factor in the invasive abilities of cancer cells.

Cell Adhesion↗
PubMed2001

Molecular mechanisms contributing to necrotizing enterocolitis.

OBJECTIVE: To examine the cellular mechanisms involved in the pathogenesis of necrotizing enterocolitis (NEC). SUMMARY BACKGROUND DATA: Necrotizing enterocolitis is a major cause of death and complications in neonates; the cellular mechanisms responsible for NEC are unknown. The inducible form of cyclooxygenase (i.e., COX-2) is activated by the transcription factor nuclear factor (NF)-kappaB and is thought to play a role in inflammation. METHODS: Segments of perforated and adjacent uninvolved small intestine from neonates with NEC were analyzed for COX-2 expression by immunohistochemistry. NEC was induced in weanling (18 days old) rats by occlusion of superior mesenteric vessels for 1 hour and intraluminal injection of platelet activating factor (50 micro/kg). Small intestine was harvested for protein extraction. Western immunoblot was performed to determine expression of COX-2. Gel shift assays were performed to assess NF-kappaB binding activity. RESULTS: Immunohistochemical analysis showed increased COX-2 protein expression in the perforated intestinal sections of all 36 neonates but not in adjacent normal intestine. Increased expression of COX-2 protein and NF-kappaB binding activity was noted in the small intestine of weanling rats at 0 and 3 hours after induction of NEC. CONCLUSIONS: Increased COX-2 expression was identified in all neonatal intestinal segments resected for perforated NEC. In addition, a coordinate induction of COX-2 expression and NF-kappaB binding was noted in a rodent model of NEC. These findings suggest that the COX-2/NF-kappaB pathway may play a role in the pathogenesis of NEC. Therapeutic agents that target this pathway may prove useful in the treatment or possible prevention of NEC.

Animals↗
PubMed2001

Postoperative pain management using intravenous patient-controlled analgesia for pediatric patients.

Pain control is an important consideration after any surgical procedures. Especially in children, more attention and care are needed during the period of postoperative pain control, which must be both sufficiently safe and effective. In this respect, intravenous patient-controlled analgesia provides improved titration of analgesic drugs, thereby maintaining optimal analgesic status with few side effects. Thirty pediatric patients were randomly divided into two groups: the intravenous patient-controlled analgesia group (with nalbuphine HCl and ketorolac tromethamine) and the conventional pethidine HCl intramuscular group. The degree of analgesia was assessed every 4 hours until the second postoperative day. The intravenous patient-controlled analgesia group had significantly lower pain scores and took less time until they were able to walk to the bathroom, but as many side effects as the control group. We concluded that intravenous patient-controlled analgesia is safe and effective for pediatric patients who have moderate to severe pain after operations such as rib cartilage graft, iliac bone graft, and large flap surgeries.

Analgesia, Patient-Controlled↗
PubMed2001

A longitudinal evaluation of an educational software program: a case study of Urinalysis-Tutor.

PURPOSE: To examine students' learning before and after revising an educational software program and to explore students' patterns of use of an interactive feature that compares images. METHOD: Study participants were 466 University of Washington School of Medicine students. Two cohorts of students (one in 1996 and one in 1997) used the original version of the software. Following analysis of the students' learning, the software program was modified based on instructional design principles pertaining to visual learning and concept acquisition. A 1998 cohort of students used the revised program and their performance was compared with that of the 1996 cohort. Analyses were based on pre- and post-test scores, data collected from the observation of students, and navigational pathways tracked by the program. RESULTS: There was very little difference in the overall performances of the students who used the original program and those who used the revised program. Error analysis focusing on 11 conceptual areas showed that reductions in errors occurred for six of 11 concepts, with statistically significant reductions of errors for two concepts. Additional navigational data collected in 1998 showed that students used an interactive feature for comparing images in different patterns. The data showed a positive association between performance and the anchored viewing mode of image display. CONCLUSIONS: While this study cannot point to specific design components that facilitated or hindered learning, it demonstrated a potential benefit of linking usage-pattern data and performance. Future studies should evaluate design factors that affect usage patterns and performances based on navigational data collected while students interact with software programs.

Cohort Studies↗
PubMed2001

Abdominal migraine in children with neurofibromatosis type 1: a case series and review of gastrointestinal involvement in NF1.

BACKGROUND: Symptomatic involvement of the gastrointestinal tract in children with neurofibromatosis type 1 (NF1) is rare. Most reported complications in adults are caused by the presence of neurofibromas in the stomach, small bowel, or mesentery. In contrast, abdominal pain in children with NF1 may be the result of nonanatomic causes, such as migraine. There are no previous reports of an association between abdominal migraine and NF1. METHODS: Children with abdominal migraine were identified from a group of children with NF1, all of whom had been followed up for a minimum of 3 years. Medical records of cases were reviewed independently by two authors. MEDLINE was searched via PubMed for all reports of children with NF1 and any associated gastrointestinal involvement. RESULTS: Six children with NF1 and intermittent, episodic, severe abdominal pain are reported. Investigations for obstructive or inflammatory causes of abdominal pain were negative. All patients had previously been diagnosed with migraine headaches by a neurologist. In five of the six patients, propranolol (10-15 mg three times daily) resulted in relief of their abdominal pain within days of starting therapy. Our review identified 24 children in the medical literature with gastrointestinal complications of NF1, mostly secondary to visceral neurofibromas. In almost all of these cases, clinical examination and simple radiologic investigations led to the definitive diagnosis. There were no reports of abdominal migraine complicating NF1. CONCLUSIONS: Abdominal pain secondary to migraine is an unrecognized cause of abdominal pain in children with NF1 and may be more common than anatomic causes of abdominal pain in children with NF1. In children with NF1 and severe recurrent abdominal pain in whom an evaluation for anatomic lesions is negative, a trial of migraine therapy may be indicated.

Abdominal Pain↗
PubMed2001

Peroxisome proliferator-activated receptor-gamma ligands inhibit nuclear but not cytosolic extracellular signal-regulated kinase/mitogen-activated protein kinase-regulated steps in vascular smooth muscle cell migration.

Vascular smooth muscle cell (VSMC) migration involves adhesion, locomotion, and invasion regulated by various signaling molecules, among which the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) play a critical role. We have shown that the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands troglitazone and rosiglitazone inhibit VSMC migration downstream of ERK MAPK. The purpose of the current study was to more specifically determine which step(s) in VSMC migration are targeted by inhibition of the ERK MAPK pathway or activation of PPAR-gamma. VSMC adhesion was not affected by the ERK MAPK pathway inhibitor PD98059 or PPAR-gamma ligands. Phosphorylation and activation of myosin light chain kinase (MLCK) play important roles in cell locomotion. Platelet-derived growth factor (PDGF)-induced MLCK phosphorylation (1.7-fold) was completely blocked by PD98059 at 30 microM (p < 0.05), but not by troglitazone or rosiglitazone. PDGF-directed migration (5.8-fold) was inhibited by PD98059 (-88% at 30 microM) and the MLCK inhibitor ML9 (0.1-1 microM, -84% at 1 microM) (all p < 0.05). The transcription factor Ets-1 mediates matrix metalloproteinase induction required for tissue invasion by VSMC. PDGF (20 ng/ml) stimulated an Ets-1 protein expression (14-fold at 60 min) in VSMC, which was inhibited by PD98059 (-72% at 30 microM), troglitazone (-69% at 20 microM), and rosiglitazone (-54% at 10 microM) (all p < 0.05). Immunohistochemistry of rat aortae 2 h after balloon injury showed a dramatic upregulation of Ets-1, which was markedly inhibited in animals that had received troglitazone treatment. In contrast, phosphorylated ERK MAPK was not affected by troglitazone. These data are consistent with PPAR-gamma ligands exerting their anti-migratory effects downstream of ERK MAPK activation by blocking nuclear events, such as Ets-1 expression, required for cell invasion in response to arterial injury.

Animals↗
PubMed2001

Therapeutic effects of sodium butyrate on glioma cells in vitro and in the rat C6 glioma model.

OBJECTIVE: Preliminary in vitro studies have indicated that sodium butyrate inhibits the proliferation of cultured glioma cells and induces cellular differentiation, making it potentially useful as a therapeutic agent for patients with glioblastoma multiforme. The purpose of this study was to expand on the preliminary research by investigating the effects of sodium butyrate on multiple cell lines, explanted cells from glioblastoma tumor specimens, and in vivo in the rat C6 glioma brain tumor model. METHODS: Four malignant glioma cell lines (A-172, T98G, U118MG, and C6) and two primary cell cultures derived from human glioblastoma tumor specimens were treated with 2 mmol/L sodium butyrate for up to 72 hours. Sodium butyrate-induced effects on cell morphology, proliferation, cell cycle distribution, migration, glial fibrillary acidic protein staining, and S100beta protein content were determined. For in vivo studies, a total of 64 male Wistar-Furth rats underwent operations to implant C6 glioma cells stereotactically or were used as controls. The rats were treated with escalating doses of sodium butyrate by microinfusion with Alzet minipumps (Durect Corp., Cupertino, CA). RESULTS: Sodium butyrate treatment in vitro produced changes in morphology and glial fibrillary acidic protein expression indicative of cellular differentiation. In cell lines and explanted cells, sodium butyrate consistently inhibited glioblastoma cell proliferation (to 51 +/- 6% that of controls) and migration (to 46 +/- 17%). Intratumoral infusion of 40 mmol/L sodium butyrate prolonged the survival of Wistar-Furth rats with intracerebral C6 tumors (P = 0.013) without detectable toxicity. CONCLUSION: These data support further consideration of direct interstitial infusion of sodium butyrate in a Phase I clinical study for patients with recurrent glioblastoma multiforme.

Animals↗
PubMed2001

Epstein-Barr virus burden in adolescents with systemic lupus erythematosus.

OBJECTIVE: We sought to determine whether patients with systemic lupus erythematosus (SLE) and a presumed primary or reactivated Epstein-Barr virus (EBV) serologic response had evidence of an active EBV infection. BACKGROUND: Patients with SLE often have what appears to be a primary or reactivated EBV serologic response. If these patients then present with fever, fatigue, adenopathy or leukopenia, it is not clear whether these symptoms are caused by worsening SLE or EBV infection. Establishing the correct diagnosis is crucial for management. METHODS: We examined the EBV burden in 13 adolescents with SLE and a presumed primary or reactivated EBV serologic response. All were taking prednisone; 2 each were also on azathioprine or intravenous pulse cyclophosphamide. EBV serologies were performed for all, and EBV burdens were assessed via immortalization assays and EBV DNA amplification of blood and saliva at least once. RESULTS: Seven patients had serologic patterns indicative of a primary EBV infection, while six had serologies indicative of a reactivated (secondary) EBV infection. Two of the latter were the only ones in whom a small amount of biologically active EBV was detected. CONCLUSION: In our series active EBV infection was not seen in most patients, despite serologic data that could be interpreted as a primary or reactivated infection. Thus the serologic profiles were more likely a consequence of immune dysregulation secondary to SLE or its therapy rather than rampant infection with EBV.

Adolescent↗
PubMed2001

Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression.

Uteroglobin (UG) is an anti-inflammatory/immunomodulatory protein. Targeted disruption of UG rendered mouse glomerulonephritis resembling immunoglobulin (Ig)A nephropathy (IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide (A to G) from the transcription initiation site of UG exon 1 would impact the progression of IgA nephropathy (IgAN). Polymerase chain reaction-restriction fragment length polymorphism and single-strand conformation polymorphism were instituted to determine the genetic polymorphism. Luciferase assay was performed using the gene constructs containing a region 404-bp long located upstream of UG exon 1 initiation site to analyse whether this polymorphism would affect the expression level. UG polymorphism was distributed no differently in patients with IgAN (n = 111) compared to 60 healthy control subjects. An excess of A genotype was found in one patient having progressive disease (P = 0.03) and the risk for the disease progression increased as the number of A alleles increased (P for trend = 0.03) after follow-up for 116 months. The odds ratio for progression with the AA genotype was 4.9 (95% Cl = 1.0-23.9) compared to patients having the GG genotype. Significant interactive effects of hypertension and genetic polymorphisms of UG on the disease progression were observed (P for interaction = 0.001). In the luciferase assay, the gene construct with A at the 38th site showed a decreased activity of 74 +/- 8.4% compared to that showed by G gene construct. Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN and may modulate the level of protein expression.

5' Untranslated Regions↗
PubMed2001

Injury induces alterations in T-cell NFkappaB and AP-1 activation.

The immune dysfunction that occurs after severe injury involves major changes in T-cell-mediated immunity resulting in suppressed T-helper 1 (Th1) type responses and increased or persistent T-helper 2 (Th2) type cytokine production. Since little is known about what signaling pathways are responsible for this injury-induced phenotypic shift in T-cells, we undertook this study to address the molecular basis for injury effects on T-helper cell subset cytokine expression. Experiments were designed to test whether diminished IL-2 gene expression after thermal injury coincided with changes in the induction of IL-2 gene regulatory transcription factors. Electrophoretic mobility shift assays (EMSA) were used to screen for nuclear expression of changes of the IL-2 gene transcription factors. Our findings revealed that changes in mitogen-stimulated T-cell AP-1 and NFkappaB factor activation correlated directly with defective mitogen-induced IL-2 mRNA expression. We determined that there was a loss of nuclear AP-1 activation and changes in NFkappaB factor activation at 9 days after injury. T-cell nuclear extracts prepared from sham injured mice showed induction of NFkappaB2 (p52) and RelA (p65) containing NFkappaB EMSA complexes, while we detected no RelA or NFkappaB2 in EMSA complexes using T-cell nuclear extracts prepared from burn injured mice. Instead, these NFkappaB EMSA complexes contained mostly NFkappaB1 (p50). Western immunoblot analysis confirmed defective nuclear RelA translocation. Taken together, these results indicate that T-cell NFkappaB and AP-1 activation pathways may be involved in the injury-induced changes in T-cell cytokine production and the immune deviation that occurs after injury.

Animals↗
PubMed2001

Structure of the transmembrane region of the M2 protein H(+) channel.

The transmembrane domain of the M2 protein from influenza A virus forms a nearly uniform and ideal helix in a liquid crystalline bilayer environment. The exposure of the hydrophilic backbone structure is minimized through uniform hydrogen bond geometry imposed by the low dielectric lipid environment. A high-resolution structure of the monomer backbone and a detailed description of its orientation with respect to the bilayer were achieved using orientational restraints from solid-state NMR. With this unique information, the tetrameric structure of this H(+) channel is constrained substantially. Features of numerous published models are discussed in light of the experimental structure of the monomer and derived features of the tetrameric bundle.

Influenza A virus↗
PubMed2001

Trends in diet, nutritional status, and diet-related noncommunicable diseases in China and India: the economic costs of the nutrition transition.

Undernutrition is being rapidly reduced in India and China. In both countries the diet is shifting toward higher fat and lower carbohydrate content. Distinct features are high intakes of foods from animal sources and edible oils in China, and high intakes of dairy and added sugar in India. The proportion of overweight is increasing very rapidly in China among all adults; in India the shift is most pronounced among urban residents and high-income rural residents. Hypertension and stroke are relatively higher in China and adult-onset diabetes is relatively higher in India. Established economic techniques were used to measure and project the costs of undernutrition and diet-related noncommunicable diseases in 1995 and 2025. Current WHO mortality projections of diet-related noncommunicable diseases, dietary and body composition survey data, and national data sets of hospital costs for healthcare, are used for the economic analyses. In 1995, China's costs of undernutrition and costs of diet-related noncommunicable diseases were of similar magnitude, but there will be a rapid increase in the costs and prevalence of diet-related noncommunicable diseases by 2025. By contrast with China, India's costs of undernutrition will continue to decline, but undernutrition costs did surpass overnutrition diet-related noncommunicable disease costs in 1995. India's rapid increase in diet-related noncommunicable diseases and their costs projects similar economic costs of undernutrition and overnutrition by 2025.

China↗
PubMed2001

Controlled cell deformation produces defined areas of contact between cells and ligand-coated surfaces.

A method which allows precise control of the time of initiation and the area of contact of T cells with immobilized ligands has been developed. Cells are trapped in an asymmetric film that can be quantitatively thinned by reducing the film's capillary pressure. Ligands adsorbed to the base of the apparatus are forced into close contact with the cells as the air-liquid interface is drawn down. Using interference microscopy and microbeads to indicate the film height, the amount of thinning can be controlled to within 1 microm. In this study, this system was used to produce contact areas of 182 and 356 microm2 between T cells and anti-CD3 coated surfaces. These contact areas were measured using fluorescent dye exclusion microscopy. This apparatus can be used for quantitative studies of T cell activation, as is reported in Patrick et al., J. Immunol. Method. 24:97-108, 2000.

Animals↗
PubMed2001

Modeling of early events in T cell signal transduction after controlled T cell activation by peptide major histocompatibility complex.

Calcium signaling was observed in murine T cells over time, starting at a precise moment of contact with a layer of fibroblasts expressing a stimulatory major histocompatibility class II-peptide complex. The contact was controlled by a film-thinning apparatus. Intracellular calcium levels were followed with the ratiometric dye, Fura-2. The calcium response was highly synchronized and well fitted by a mathematical model. The model includes three components: a sequence of reactions occurring after T cell receptor (TCR) triggering; InsP3-mediated calcium release from intracellular stores (Meyer and Stryer, Proc. Natl. Acad. Sci. USA 85: 5051-5055, 1988); and slow changes in levels phospholipase C-gammal (PLCgammal) reflecting a decrease in receptor triggering rate. Each component in the model controls a different part of the response-the initial delay, the sharp rise, and the slow decay, respectively. Kinetic parameters determined from curve fitting were the initial delay in calcium signaling defined as the time when [PLCgammal] reached its half of its maximum (76 s), the coefficient characterizing calcium efflux from endoplasmic reticulum (ER) (2.86 microM s(-1), expressed per liter of cell volume), and a rate constant characterizing the diminishing yield of production of PLCgammal (0.00046 s(-1)) by active TCR. Only the parameter representing PLCgammal production varied much from cell to cell.

Animals↗
PubMed2001

Data preprocessing and partial least squares regression analysis for reagentless determination of hemoglobin concentrations using conventional and total transmission spectroscopy.

Visible-near infrared spectroscopy was successfully used for the determination of total hemoglobin concentration in whole blood. Absorption spectra of whole blood samples, whose hemoglobin concentrations ranged between 6.6 and 17.2 g/dL, were measured from 500 to 800 nm. Two different types of transmission were measured: conventional transmission spectroscopy which collected primarily collimated radiation transmitted through the sample, and total transmission spectroscopy which used an integrating sphere to collect all scattered light as well. Different preprocessing techniques in conjunction with a partial least squares regression calibration model to predict hemoglobin concentrations were applied to the above two types of transmission. Depending on different preprocessing methods, the standard error of predictions ranged from 0.37 to 2.67 g/dL. Mean centering gave the most accurate prediction in our particular data set. Preprocessing methods designed for compensation of the scattering effect produced the worst results contrary to expectations. For univariate analysis, better prediction was achieved by total transmission measurement than by conventional transmission measurement. No significant difference was observed for multivariate analysis on the other hand. Careful selection of the data preprocessing methods and of the multivariate statistical model is required for reagentless determination of hemoglobin concentration in whole blood.

Hemoglobins↗