Biomedical subjects

E Kim

Publications and source records attributed to E Kim.

At least 73 records · Page 4Linked to original sources

PubMed2001

Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor.

BACKGROUND/PURPOSE: Antibody to vascular endothelial growth factor (anti-VEGF) suppresses tumor growth and metastasis in experimental Wilms tumor. However, tumor growth accelerates if antibody is withdrawn. As recently shown, low-dose, frequently administered topotecan, a topoisomerase-1 inhibitor, has anti-angiogenic activity. The authors hypothesized that combined topotecan/anti-VEGF therapy would suppress tumor growth and metastasis more durably than either agent alone. METHODS: Xenografts were induced by intrarenal injection of human Wilms tumor cells in athymic mice (n = 59). Mice were divided into control (n = 10), anti-VEGF (n = 16), topotecan (n = 17), and topotecan plus anti-VEGF (n = 16) groups. All control and half the treated mice were killed at week 6. Remaining ("rebound") mice were maintained without treatment until week 8. Tumor vasculature was mapped by fluorescein angiography/PECAM immunostaining. Endothelial apoptosis was assessed by TUNEL assay. RESULTS: 6 weeks: Tumor weights were reduced significantly in treated mice (P <.003 v control). Seven of ten control and 1 of 25 treated mice displayed lung metastases (P <.003). Rebound tumors were largest in topotecan-only, intermediate in antibody-treated, and smallest in combination-treated mice. Immunostaining and angiography results showed sparse vascularity in treated xenografts. Endothelial apoptosis was observed only in treated tumors. CONCLUSION: Combination low-dose topotecan and anti-VEGF antibody therapy is antiangiogenic and suppresses tumor growth and metastasis in experimental Wilms tumor more durably than either agent alone.

Animals↗

PubMed2001

Effective therapy of a vascular tumor of infancy with vincristine.

Vascular tumors are common in infancy, affecting as many as 10% of children. These lesions often follow a benign course, with an initial proliferative phase followed by spontaneous involution, and require no therapy. Others manifest explosive early growth and Kasabach-Merritt phenomenon, requiring therapeutic intervention. Occasionally, some bulky tumors threaten life or vision because of mass effect, also mandating intervention. Steroids are the mainstay of therapy, but often are ineffective. Interferon alpha (2a and 2b) has been used as second-line therapy in cases of steroid failure. However, interferon therapy has been associated with a significant incidence of spastic diplegia. The authors present the case of a 3-month-old girl in whom respiratory distress secondary to tracheal compression developed. Magnetic resonance imaging and magnetic resonance angiography showed a large cervicothoracic lesion encasing the great vessels and displacing the airway. She did not display associated Kasabach-Merritt phenomenon. The lesion proved refractory to standard steroid therapy, but responded dramatically to 4 cycles of vincristine (0.05 mg/kg). Although this agent has been used in children with life-threatening Kasabach-Merritt phenomenon, this is the first time it has been described in the setting of compromised vital function. Vinca alkaloids recently have been shown to have potent antiangiogenic activities in experimental models. Given the low predicted incidence of side effects at this dose, vincristine used as an antiangiogenic agent may prove an attractive alternative therapy for patients with life-threatening vascular tumors of infancy.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Novel use of an established agent: Topotecan is anti-angiogenic in experimental Wilms tumor.

BACKGROUND/PURPOSE: Antiangiogenic agents offer a new approach to the treatment of aggressive neoplasms, yet very few agents are available for current use. The authors have shown previously the efficacy of antiangiogenic therapy in experimental Wilms tumor, using an investigative antibody. They hypothesized that topotecan, administered in a regimen targeting endothelial cells, would suppress tumor growth and angiogenesis in experimental Wilms tumor. METHODS: Experimental tumors were induced in the left kidneys of athymic mice by injection of cultured Wilms tumor cells. Topotecan (0.36, 0.6, 1.0, 2.0, and 3.0 mg/kg) or vehicle was injected intraperitoneally in 2 cycles over a 6-week period. Fluorescein angiograms and platelet endothelial cell adhesion molecule-1 staining of primary tumors were performed to ascertain vascular architecture. Endothelial apoptosis was assessed by TdT-mediated dUTP nick end labeling assay. RESULTS: Tumor weights were reduced significantly in treated versus control animals, even in the lowest-dose group. Endothelial cell staining and angiography results showed relatively sparse vascularity in treated xenografts. Endothelial apoptosis was observed in treated but not control tumors. CONCLUSIONS: Topotecan, delivered in an "antiangiogenic" regimen, even at very low doses, significantly inhibited growth of experimental Wilms tumors. No adverse effects were noted at low doses. Thus, the established chemotherapy agent topotecan may be useful in a novel role: as antiangiogenic therapy. J Pediatr Surg 36:1781-1784.

Angiogenesis Inhibitors↗

PubMed2001

Retained neuropsychological abilities of individuals with Alzheimer's disease.

Individuals with Alzheimer's disease (AD) retain certain cognitive abilities over the course of the disease. In this article, we describe retained cognitive-linguistic abilities and the status of activities of daily living (ADLs) of individuals in the early, middle, and late stages of AD. Knowledge of preserved abilities in AD is necessary for clinicians to structure communication-stimulation programs and to train caregivers in the most effective ways to facilitate communication. Using the Global Deterioration Scale (GDS) for staging severity of AD, an outline of preserved abilities by disease stage is provided. Attention, memory, and communication abilities are discussed, and samples of discourse from patients at different stages are included.

Activities of Daily Living↗

PubMed2001

Development of a breast self-examination program for the Internet: health information for Korean women.

Internet-based health information will enable us to interact with many people despite distance and time constraints. Informational media by computer is expected to become an important factor that affects health behavior. This study was done to develop an accessible multimedia program about breast self-examination on the Internet. This study was designed by using the two steps of need assessment and program development. For the need assessment step, a survey was carried out. The sample consisted of the 82 women of Yonsei University selected by convenient random sampling. At the program development step, screen design took into account perspectives of computer engineering. A storyboard for every screen was made via screen design and then ported to computer using the Netscape Navigator program. A breast self-examination program was developed using Netscape 4.0 on the Windows 98 platform. The multimedia program, including text, graphics, animation, and sound, was constructed with HTML language using Memo Sheet in Netscape Navigator. The contents of health information posted on the Internet included general information about breast cancer, the importance of breast self-examination, self-risk appraisal of breast cancer, the diverse methods about breast self-examination, the monthly check list graph, and social network for consultation. It is possible to interact with clients through the Question and Answer function on screen. This Internet-based health information program provides enough information, which can be accessed using search systems on the Internet.

Adult↗

PubMed2001

Intraocular lens power calculation after laser in situ keratomileusis for myopia and hyperopia: a standardized approach.

PURPOSE: (1) To determine the effect of myopic and hyperopic laser in situ keratomileusis (LASIK) on calculation of intraocular lens (IOL) power. (2) To determine a standard way to approach the IOL power determination after LASIK, and (3) To compare different suggested methods. METHODS: Biometric analysis and theoretical calculation of IOL powers for eyes undergoing LASIK for myopia and hyperopia were performed. RESULTS: Manual keratometry after LASIK for myopia resulted in underestimation of IOL power. Manual keratometry after hyperopic LASIK resulted in overestimation of IOL power. The amount of error was directly related to the amount of correction by LASIK. CONCLUSION: The pre-LASIK refraction can be used theoretically to determine an accurate IOL power.

Cataract Extraction↗

PubMed2001

Modulation of Chelidonii herba on GABA activated chloride current in rat PAG neurons.

Modulation of Chelidonii herba on gamma-aminobutyric acid (GABA) activated chloride current in the acutely dissociated periaqueductal gray (PAG) neuron was studied by nystatin-perforated patch-clamp technique. High concentrations of Chelidonii herba elicited ion current, that was blocked by bicuculline. Low concentrations reduced the GABA activated current in PAG. Two types of inhibitory action of Chelidonii herba on GABA activated current have been implicated in PAG. One is the inhibitory action of Chelidonii herba on GABA was abolished by naltrexone and the other is that of Chelidonii herba was potentiated by naltrexone. In addition, all of two types of action of Chelidonii herba are linked to pertussis toxin-sensitive GTP-binding proteins. These results suggest that the inhibitory modulation of Chelidonii herba on GABA activated current via G-proteins in PAG neuron is an important analgesic mechanism.

Animals↗

PubMed2001

Effects of gamma-irradiated fats on plasma lipid concentrations and hepatic cholesterol metabolism in rats.

Currently, there is a growing need for food irradiation that is effective in food preservation and quality improvement. Accordingly, this study was designed to observe the effects of gamma-irradiated dietary fat on plasma lipid concentrations and hepatic cholesterol metabolism in rats. Male rats were fed 5-kGy-gamma-irradiated beef tallow (gammaBT), corn oil (gammaCO), perilla oil (gammaPO), and nonirradiated fats (BT, CO, and PO) for 6 weeks. The gamma-irradiated fat feeding did not affect the plasma lipid concentrations. However, the hepatic cholesterol content was significantly higher in the rats fed gamma-CO as compared with the rats fed nonirradiated CO (40.0 vs. 28.2 mg/g liver). The hepatic HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activities were not significantly different between the controls and the gamma-irradiated fat fed groups. However, the hepatic ACAT (acyl-CoA:cholesterol acyltransferase) activity was significantly lower in the gammaPO group as compared with its control group (138.2 vs. 404.5 pmol min(-1) mg(-1)). Among the nonirradiated groups, the ACAT activities of the CO and PO groups were higher than that of the BT group. The amounts of coprostanone, cholesterol, and total fecal neutral sterol were significantly higher in the gammaPO group as compared with the other groups. These results indicate that although slight changes in the lipid metabolism were observed as a result of 5-kGy-gamma-irradiated fat feeding, they were relative to the fat type and had no harmful consequences.

Animals↗

PubMed2001

Statistical optimization of bioluminescence of Photobacterium phosphoreum KCTC2852.

In this study, media optimization by statistically designed experiments stimulated an increase in the intensity and stability of bioluminescence of Photobacterium phosphoreum KCTC 2852 during continuous cultivation. The Plackett-Burman design method selected two components (NaCl, yeast extract) among nine components of the seawater complete (SC) medium. The response-surface design method calculated the optimum concentration of NaCl (31.1 g/l) and yeast extract (5.1 g/l). In the optimized medium, bioluminescence per cell increased twofold. During continuous cultivation in a stirred tank reactor, bioluminescence decreased rapidly in the SC medium, whereas the optimized medium could maintain bioluminescence for more than 80 h, resulting in an increased bioluminescence. Upon contact with 0.1 ppm Hg2+, a sharp decrease in bioluminescence was observed, which was reproducible in the measuring chamber. This shows the possibility that P. phosphoreum could be cultivated continuously with enhanced bioluminescence stability and that on-line water toxicity could be monitored continuously.

Journal Article↗

PubMed2001

Proteasome inhibitors differentially affect heat shock protein response in cancer cells.

The heat shock proteins (HSPs) are molecular chaperones that are emerging as biochemical regulators of cell growth, apoptosis, protein homeostasis and intracellular targeting of peptides. The immunological function of the HSPs are imparted by tissue specific peptides associated with the HSPs and as such autologous cancer derived HSP-peptide complexes are unique therapeutic agents. Since a majority of the intracellular peptides are generated by the proteasome, we examined the consequence of abrogation of proteasome function by proteasome inhibitors (PIs) such as Lactacystin, MG-132 and LLM on the growth and induction profile of HSP70 and gp96 using hematopoietic, lymphoid, and epithelial derived cancer cell lines. The effect on growth was measured by the XTT assay and induction of the heat shock proteins by western blot analyses using HSP70 and gp96 specific antibodies. Of the PIs tested, cancer cells, were most sensitive to MG-132 and least sensitive to LLM. MG-132 also showed a 10-fold differential sensitivity between estrogen receptor positive, (ER+) MCF-7 cells and negative cells, (ER-) MDA-MB-231. Induction of heat shock proteins, gp96 and HSP70 was, however, noted in response to LLM. Since LLM exhibited minimal cytotoxic effect, metabolic stress that results in induction of HSPs may not be translated in cell growth inhibition and that there may exist a cell-type specific phenomenon in the HSP response to PI mediated metabolic stress.

Acetylcysteine↗

PubMed2001

Predicting the rotationally neutral state of the femur by comparing the shape of the contralateral lesser trochanter.

The rotationally neutral state of the femur was measured by comparing the shape of the contralateral lesser trochanter in 100 adults. Three observers predicted a position presumed to be neutral by comparing the shape of the neutrally positioned contralateral lesser trochanter previously recorded by C-arm image intensification. The mean (SD) angular discrepancy between the neutral point and the predicted angle was 3.4 degrees (+/- 2.4) without interobserver variation (P = .87). Seventy-seven percent indicated the value within 4 degrees, and none of the observations exceeded 15 degrees. These findings suggest the outline of the contralateral lesser trochanter may be a useful reference during surgical treatment of femoral fractures to minimize rotational deformity.

Adult↗

PubMed2001

Heparin binding protein (CAP37) differentially modulates endotoxin-induced cytokine production.

BACKGROUND AND OBJECTIVE: CAP37, also known as heparin-binding protein (HBP), is neutrophil-derived protein with multifunctional properties that include monocyte chemotaxis and the enhancement of LPS-induced tumor necrosis factor (TNF-alpha), IL-1, IL-6, and PGE2production from isolated monocytes, which suggest a generalized effect on LPS-induced monocyte activation. In this study, we tested whether HBP amplifies the release of other LPS-responsive cytokines from isolated human monocytes. METHODS: Freshly isolated monocytes from 5 healthy donors were stimulated for 24 h with saline, LPS (10 ng/ml), HBP (10 microg/ml), or a combination of LPS + HBP. Cytokine levels in the supernate were measured with ELISA. ANOVA and Fisher's posthoc test were used to determine significance (p < 0.05). Differential display was used to assess cellular mRNA levels. RESULTS: HBP alone induced the production of IL-8, macrophage inhibitory protein MIP-1alpha, and TNF-alpha. HBP increased the LPS-induced production of IL-8, MIP-1alpha, TNF-alpha, IL-1beta, but HBP did not increase the significant LPS-induced release of IL-10, monocyte chemoattractant protein MCP-1, and IL- 12. Differential display demonstrated that HBP induced an mRNA pattern that was different from the mRNA pattern induced by saline, LPS, or HBP + LPS, indicating multiple and different gene activation. CONCLUSIONS: We conclude that HBP is not a general amplificator of LPS-induced monocyte activation but rather a molecule that targets the production of a distinct set of mediators including pro-inflammatory cytokines such as TNF-alpha and IL-1beta, but not the anti-inflammatory cytokine IL-10, nor IL-12 and MCP-1. The exact intracellular signaling pathways remain unknown but include mechanisms that alter gene transcription.

Analysis of Variance↗

PubMed2000

Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9.

Sentrin is a ubiquitin-like protein that can covalently modify cellular proteins, and is a Fas binding protein that protects cells against anti-Fas induced cell death. However, the mechanism by which sentrin exerts its effect upon Fas-mediated apoptosis is not well known. Thus, this study examined the interaction of sentrin with Daxx. Sentrin interacted with Daxx but not with FADD when analyzed by yeast two-hybrid assay. In vitro translated Daxx bound to GST-sentrin fusion protein. FLAG-sentrin fusion protein was also coimmunoprecipitated with Daxx in BOSC23 cells. Also, Daxx interacted with Ubc9, an essential protein as a key conjugating enzyme. Amino acids 625-740 of Daxx, known as Fas binding region, was also mapped as sentrin and Ubc9 binding region. Colocalization of Fas, sentrin, and Ubc9 binding regions suggests the importance of that region upon the regulation of Daxx. Our data also demonstrated that sentrin could homooligomerize by protein-protein interaction.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Human Fas associated factor 1, hFAF1, gene maps to chromosome band 1p32.

Human Fas associated factor 1 protein (hFAF1) is involved in the positive regulation of Fas signaling even though it can not initiate the signal for itself. By chromosomal assignment using somatic cell hybrids (CASH), the hFAF1 gene was located on human chromosome 1 between markers D1S443 and D1S197. The hFAF1 gene was mapped to human chromosome band 1p32 by FISH utilizing a genomic PAC clone containing the gene. In genomic Southern analysis using hFAF1 cDNA as a probe, several bands appeared in three different restriction enzyme digestions. The single band appearance in FISH analysis compared to several bands in Southern blots implies that the hFAF1 gene would be rather big or that an additional hFAF1 gene isotype(s) might be present in close vicinity.

3' Untranslated Regions↗

PubMed2000

The mechanism of phospholipase C-gamma1 regulation.

Phospholipase C (PLC)1 hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate the second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces a transient increase in intracellular free Ca2+, while DAG directly activates protein kinase C. Upon stimulation of cells with growth factors, PLC-gamma1 is activated upon their association with and phosphorylation by receptor and non-receptor tyrosine kinases. In this review, we will focus on the activation mechanism and regulatory function of PLC-gamma1.

Cell Division↗

PubMed2000

14-3-3 interacts with regulator of G protein signaling proteins and modulates their activity.

Regulator of G protein signaling (RGS) proteins function as GTPase-activating proteins (GAPs) that stimulate the inactivation of heterotrimeric G proteins. We have recently shown that RGS proteins may be regulated on a post-translational level (Benzing, T., Brandes, R., Sellin, L., Schermer, B., Lecker, S., Walz, G., and Kim, E. (1999) Nat. Med. 5, 913-918). However, mechanisms controlling the GAP activity of RGS proteins are poorly understood. Here we show that 14-3-3 proteins associate with RGS7 and RGS3. Binding of 14-3-3 is mediated by a conserved phosphoserine located in the Galpha-interacting portion of the RGS domain; interaction with 14-3-3 inhibits the GAP activity of RGS7, depends upon phosphorylation of a conserved residue within the RGS domain, and results in inhibition of GAP function. Collectively, these data indicate that phosphorylation-dependent binding of 14-3-3 may act as molecular switch that controls the GAP activity keeping a substantial fraction of RGS proteins in a dormant state.

14-3-3 Proteins↗

PubMed2000

Heterogeneous nuclear ribonucleoproteins as regulators of gene expression through interactions with the human thymidine kinase promoter.

In search for nuclear proteins that interact with the human thymidine kinase (htk) promoter, we discovered that p37AUF, a hnRNP C-like protein, and hnRNP A1, both members of the heterogeneous ribonucleoprotein family, can bind with high affinity to an ATTT sequence motif contained within the cell cycle regulatory unit (CCRU). We report here that over-expression of p37AUF stimulates gene expression mediated by the htk promoter in a promoter-sequence specific manner, whereas hnRNP A1 suppresses it. Both recombinant p37AUF and hnRNP A1 can bind the htk CCRU, suggesting that their binding to the DNA target does not require additional cellular components. We further discovered that hnRNP K is a potent suppressor of htk mediated gene activity. However, its mechanism of action is mediated through protein-protein interaction, since hnRNP K itself cannot bind the htk CCRU but can competitively inhibit the binding of other hnRNPs. The binding site for the hnRNPs on the htk CCRU is not required for S-phase induction of the htk promoter. However, in stable but not transient transfectants, the mutation of the hnRNP binding site results in 5- to 10-fold reduction of htk mediated gene activity in synchronized and exponentially growing cells. Collectively, these findings support emerging evidence that hnRNPs, in addition to their traditional role in RNA biogenesis, could be regulators of gene expression through direct DNA binding or interaction with other proteins.

Amino Acid Sequence↗

PubMed2000

Transduction effect of antisense K-ras on malignant phenotypes in gastric cancer cells.

The antitumoral effects of antisense RNA to K-ras were investigated in gastric cancer cell lines by examining the level of K-ras expression and the tumorigenicity in vitro and in vivo. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), DNA sequencing, and immunoblotting analysis revealed that YCC-1 gastric cancer cells overexpressed wild type K-ras, whereas YCC-2 cells had a homozygous mutation in codon 12 from GGT (glycine) to AGT (serine), while SNU-1 cells had a heterozygous mutation to GAT (asparagine) in the identical position. Both YCC-1 and YCC-2 cells were transduced by LNC-AS/K-ras containing the antisense 2.2 kb genomic K-ras DNA fragment covering exon 2 and exon 3 specific for K-ras. The application of antisense K-ras significantly downregulated the expression of K-ras and had no influence on the expression of either H-ras or N-ras. The antisense-transduced YCC-2 cells grew considerably slower than the control group transduced by LNCX, whereas the growth inhibition of antisense-transduced YCC-1 cells was less prominent than that of transduced YCC-2 cells. In addition, the tumorigenicity of YCC-2 cells transduced by LNC-AS/K-ras was totally lost. Therefore, our results imply that the specific inhibition of K-ras p21 protein can be accomplished by introducing the antisense covering the K-ras- specific region to gastric cancer cells with aberrant K-ras expression, resulting in a reduction of the growth rate and suppression of tumorigenicity.

Animals↗