Search

Jung Bum Choi,1,* Woo Kyung Lee,2,3,* Seul Gi Lee,2,4 Haengrang Ryu,5 Cho Rok Lee,4 Sang Wook Kang,4 Jong Ju Jeong,4 Kee-Hyun Nam,4 Eun Jig Lee,2,3 Woong Youn Chung,4 Young Suk Jo,2,3 Jandee Lee4 1Department of Surgery, Pusan National University College of Medicine, Busan, South Korea; 2Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea; 3Department of Internal Medicine, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; 4Department of Surgery, Open NBI Convergence Technology Research Laboratory, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; 5Department of Surgery, Hongik Hospital, Seoul, South Korea *These authors contributed equally to this work Purpose: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PTMC) may reduce the risk of overtreatment of clinically insignificant cancer. However, the absence of predictor for the progression of PTMC resulted in treatment delay and potentially compromising cure of aggressive disease. Therefore, to anticipate potential damage of delayed surgery, we investigated the oncologic outcomes of patients with low-risk PTMC initially eligible for AS except clinically apparent lymph node metastasis (LNM), imitating delayed surgery with neck dissection. Materials and methods: A total of 5,348 patients, enrolled between 1987 and 2016, with low-risk PTMC initially eligible for AS were included regardless of LNM. We classified our study patients into two groups: Group I, lobectomy with prophylactic central cervical node dissection; Group II, total thyroidectomy with modified radical neck dissection for LNM. In addition, we investigated the oncological outcomes of patients with second-wave surgery due to lateral lymph node recurrence (Group III, subgroup of Group I). Results: Group I showed more favorable clinicopathological characteristics compared with Group II. In Group I, only 29 (0.58%) of 4,927 patients underwent second-wave surgery with neck dissection for lateral lymph node recurrences, whereas in Group II, all 22 (5.23%) of 421 patients underwent second-wave selective node dissection because of nodal recurrence. Disease-free survival rates were significantly different between Groups I and II (P

Sang Gon Lee,1,* Chang Hyun Kim,1,* Si Woo Sung,1 Eun Seok Lee,1 Min Su Goh,1 Ho Yub Yoon,1 Myung Joo Kang,2 Sangkil Lee,3 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2College of Pharmacy, Dankook University, Chungnam, Republic of Korea; 3College of Pharmacy, Keimyung University, Daegu, Republic of Korea *These authors contributed equally to this work Background: To facilitate selective and enhanced drug delivery to hepsin (Hpn)-expressing cancer cells, RIPL peptide (IPLVVPLRRRRRRRRC, 16-mer)-conjugated nanostructured lipid carriers (RIPL-NLCs) were developed. Methods: NLCs were prepared using a solvent emulsification-evaporation method and the RIPL peptide was conjugated to the maleimide-derivatized NLCs via the thiol-maleimide reaction. Employing a fluorescent probe (DiI), in vitro target-selective intracellular uptake behaviors were observed using fluorescence microscopy and flow cytometry. Separately, docetaxel (DTX) was encapsulated by pre-loading technique, then cytotoxicity and drug release were evaluated. In vivo antitumor efficacy was investigated in BALB/c nude mice with SKOV3 cell tumors after intratumoral injections of different DTX formulations at a dose equivalent to 10 mg/kg DTX. Results: RIPL-NLCs showed positively charged nanodispersion, whereas NLCs were negatively charged. DTX was successfully encapsulated with an encapsulation efficiency and drug loading capacity of 95–98% and 44-46 µg/mg, respectively. DTX release was diffusion-controlled, revealing the best fit to the Higuchi equation. Cellular uptake of DiI-loaded RIPL-NLCs was 8.3- and 6.2-fold higher than that of DiI-loaded NLCs, in Hpn(+) SKOV3 and LNCaP cells, respectively. The translocation of RIPL-NLCs into SKOV3 cells was time-dependent with internalization within 1 h and distribution throughout the cytoplasm after 2 h. DTX-loaded RIPL-NLCs (DTX-RIPL-NLCs) revealed dose-dependent in vitro cytotoxicity, while drug-free formulations were non-cytotoxic. In SKOV3-bearing xenograft mouse model, DTX-RIPL-NLCs significantly inhibited tumor growth: the inhibition ratios of the DTX solution-treated and DTX-RIPL-NLC-treated groups were 61.4% and 91.2%, respectively, compared to those of the saline-treated group (control). Conclusion: RIPL-NLCs are good candidates for Hpn-selective drug targeting with a high loading capacity of hydrophobic drug molecules. Keywords: nanostructured lipid carriers, RIPL peptide, intracellular delivery, docetaxel, antitumor efficacy, targeting

Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity.Conclusion: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.Keywords: cathepsin B, CT26 cell, enzyme-sensitive dendrimer, tumor targeting, tetra peptide

Dong Woo Yeom,1 Ye Seul Song,1 Sung Rae Kim,1 Sang Gon Lee,1 Min Hyung Kang,1 Sangkil Lee,2 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Keimyung University, Daegu, Republic of Korea Abstract: In this study, we developed and optimized a self-microemulsifying drug delivery system (SMEDDS) formulation for improving the dissolution and oral absorption of atorvastatin calcium (ATV), a poorly water-soluble drug. Solubility and emulsification tests were performed to select a suitable combination of oil, surfactant, and cosurfactant. A d-optimal mixture design was used to optimize the concentration of components used in the SMEDDS formulation for achieving excellent physicochemical characteristics, such as small droplet size and high dissolution. The optimized ATV-loaded SMEDDS formulation containing 7.16% Capmul MCM (oil), 48.25% Tween 20 (surfactant), and 44.59% Tetraglycol (cosurfactant) significantly enhanced the dissolution rate of ATV in different types of medium, including simulated intestinal fluid, simulated gastric fluid, and distilled water, compared with ATV suspension. Good agreement was observed between predicted and experimental values for mean droplet size and percentage of the drug released in 15 minutes. Further, pharmacokinetic studies in rats showed that the optimized SMEDDS formulation considerably enhanced the oral absorption of ATV, with 3.4-fold and 4.3-fold increases in the area under the concentration-time curve and time taken to reach peak plasma concentration, respectively, when compared with the ATV suspension. Thus, we successfully developed an optimized ATV-loaded SMEDDS formulation by using the d-optimal mixture design, that could potentially be used for improving the oral absorption of poorly water-soluble drugs. Keywords: atorvastatin, SMEDDS, d-optimal mixture design, optimization, dissolution, bioavailability

Sang Gon Lee,1,* Jae Han Jeong,1,* Kyung Min Lee,1 Kyu Ho Jeong,1 Huisuk Yang,2 Miroo Kim,2 Hyungil Jung,2 Sangkil Lee,3 Young Wook Choi11College of Pharmacy, Chung-Ang University, Seoul, South Korea; 2Department of Biotechnology, Yonsei University, Seoul, South Korea; 3College of Pharmacy, Keimyung University, Daegu, South Korea *These authors contributed equally to this workAbstract: Nanostructured lipid carriers (NLCs) were employed to formulate a lipophilic drug into hydrophilic polymeric microneedles (MNs). Hyaluronic acid (HA) was selected as a hydrophilic and bioerodible polymer to fabricate MNs, and nile red (NR) was used as a model lipophilic molecule. NR-loaded NLCs were consolidated into the HA-based MNs to prepare NLC-loaded MNs (NLC-MNs). A dispersion of NLCs was prepared by high-pressure homogenization after dissolving NR in Labrafil and mixing with melted Compritol, resulting in 268 nm NLCs with a polydispersity index of 0.273. The NLC dispersion showed a controlled release of NR over 24 hours, following Hixson–Crowell's cube root law. After mixing the NLC dispersion with the HA solution, the drawing lithography method was used to fabricate NLC-MNs. The length, base diameter, and tip diameter of the NLC-MNs were approximately 350, 380, and 30 µm, respectively. Fluorescence microscopic imaging of the NLC-MNs helped confirm that the NR-loaded NLCs were distributed evenly throughout the MNs. In a skin permeation study performed using a Franz diffusion cell with minipig dorsal skin, approximately 70% of NR was localized in the skin after 24-hour application of NLC-MNs. Confocal laser scanning microscopy (z-series) of the skin at different depths showed strong fluorescence intensity in the epidermal layer, which appeared to spread out radially with the passage of time. This study indicated that incorporation of drug-loaded NLCs into MNs could represent a promising strategy for controlled dermal delivery of lipophilic drugs.Keywords: polymeric microneedles, nanostructured lipid carriers, dermal delivery, controlled release, hyaluronic acid

We report recent experimental results from HL-2A and KSTAR on ELM mitigation by supersonic molecular beam injection (SMBI). Cold particle deposition within the pedestal by SMBI is verified in both machines. The signatures of ELM mitigation by SMBI are an ELM frequency increase and ELM amplitude decrease. These persist for an SMBI influence time τI. Here, τI is the time for the SMBI influenced pedestal profile to refill. An increase in fELMSMBI/fELM0 and a decrease in the energy loss per ELM ΔWELM were achieved in both machines. Physical insight was gleaned from studies of density and vΦ (toroidal rotation velocity) evolution, particle flux and turbulence spectra, divertor heat load. The characteristic gradients of the pedestal density soften and a change in vΦ was observed during a τI time. The spectra of the edge particle flux Γ ∼ 〈ṽrñe〉 and density fluctuation with and without SMBI were measured in HL-2A and in KSTAR, respectively. A clear phenomenon observed is the decrease in divertor heat load during the τI time in HL-2A. Similar results are the profiles of saturation current density Jsat with and without SMBI in KSTAR. We note that τI/τp (particle confinement time) is close to ∼1, although there is a large difference in individual τI between the two machines. This suggests that τI is strongly related to particle-transport events. Experiments and analysis of a simple phenomenological model support the important conclusion that ELM mitigation by SMBI results from an increase in higher frequency fluctuations and transport events in the pedestal. © 2014 IAEA, Vienna.

Toroidal rotation profiles have been investigated in KSTAR H-mode plasma using combined auxiliary heating by co-neutral beam injection (NBI) and electron cyclotron resonance heating (ECH). The ion temperature and toroidal rotation are measured with x-ray imaging crystal spectroscopy and charge exchange recombination spectroscopy. H-mode plasma is achieved using co-current 1.3 MW NBI, and a 0.35 MW ECH pulse is added to the flat-top of H-mode. The core rotation profiles, which are centrally peaked in the pure NBI heating phase, flatten when ECH is injected, while the edge pedestal is unchanged. Dramatic decreases in the core toroidal rotation values (ΔVtor/V tor ∼ -30%) are observed when on-axis ECH is added to H-mode. The experimental data show that the decrease of core rotation velocity and its gradient are correlated with the increase of core electron temperature and its gradient, and also with the likely steepening of the density gradient. We thus explore the viability of a hypothesized ITG (ITG ion temperature gradient instability) → TEM (trapped electron mode instability) transition as the explanation of the observed counter-current flow induced by ECH. However, the results of linear microstability analyses using inferred profiles suggest that the TEM is excited only in the deep core, so the viability of the hypothesized explanation is not yet clear. © 2013 IAEA, Vienna.

The fourth KSTAR campaign in 2011 concentrated on active edge-localized mode (ELM) control by various methods such as non-axisymmetric magnetic perturbations, supersonic molecular beam injection (SMBI), vertical jogs of the plasma column and edge electron heating. The segmented in-vessel control coil (IVCC) system is capable of applying n2 perturbed field with different phasing among top, middle and bottom coils. Application of an n=1 perturbed field showed a desirable ELM suppression result. Fast vertical jogs of the plasma column achieved ELM pace-making and ELMs locked to 50Hz vertical jogs were observed with a high probability of phase locking. A newly installed SMBI system was used for ELM control and the state of mitigated ELMs was sustained by the optimized repetitive SMBI pulse for a few tens of ELM periods. A change in ELM behaviour was seen due to edge electron heating although the effect of ECH launch needs supplementary analyses. The ECEI images of suppressed/mitigated ELM states showed apparent differences when compared with natural ELMy states. Further analyses are ongoing to explain the observed ELM control results. © 2012 IAEA, Vienna.

Research on the spherical torus (or spherical tokamak) (ST) is being pursued to explore the scientific benefits of modifying the field line structue fro that in more moderate aspect ratio devices. The ST experiments are being conducted in various US research facilities. The area of power and particle handling is expected to be challenging because of the higher power density expected in the ST relative to that in conventional aspect-ratio tokamaks.

There are various uncommon gastrointestinal complications, as liver transplantation becomes increasingly popular as the only curative method for patients with end-stage liver diseases. It is important for radiologists evaluating postoperative liver transplantation recipients to have a perspective on the possible gastrointestinal complications after liver transplantation and their radiologic features for early detection and early treatment. This article illustrates radiologic findings and clinical features of various uncommon gastrointestinal complications after liver transplantation. [ABSTRACT FROM AUTHOR]

Propolis is a sticky, resinous material that honey bees collect from various plants, and mix with wax and other secretions. The aim of this study was to evaluate the antidiabetic effect of propolis through an analysis of the expression and enzyme activity of glucose-6-phosphatase (G6Pase) and to elucidate the mechanism by which propolis inhibits G6Pase gene expression. When HepG2 cells were incubated in high glucose media (25 mm), G6Pase expression was induced. Propolis significantly reduced the expression and enzyme activity of G6Pase; however, the hypoglycemic effect was not abolished by the phosphoinositide 3-kinase inhibitor, LY294002, and by the mitogen-activated protein kinase (MAPK) inhibitor, U0126. Propolis inhibited the activity of GSK3α and β via the inhibition of serine and tyrosine phosphorylation, specifically, Y279 for GSK3α and Y216 for GSK3β. The phosphorylations of Y279 and Y216 occur through autophosphorylation by GSK3α/β and are involved in their own activity. Although propolis showed antioxidant activity, antidiabetic effect of propolis was not influenced by hydrogen peroxide and N-acetylcysteine. These results suggest that propolis inhibits the expression of G6Pase by inhibiting the autophosphorylation of Y279 and Y216 of GSK3α and β, respectively, which are involved in the activation of GSK3. These findings suggest that propolis may be a potential antidiabetic agent for the treatment of insulin-insensitive diabetes. [ABSTRACT FROM AUTHOR]

Objectives: To examine mutations within the penA, mtrR, porB, ponA and pilQ genes of Neisseria gonorrhoeae to determine their contribution to cephalosporin resistance.Methods: A total of 46 N. gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone (MICs > or = 0.12 mg/L) and two susceptible isolates were selected. The full sequence of penA and partial sequences previously reported as hot mutation sites of the other genes were analysed. Genotyping by N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed.Results: A mosaic penicillin-binding protein 2 (PBP 2) was found in a single isolate that exhibited the highest cefixime MIC (0.5 mg/L). The majority of the isolates with reduced susceptibility to cephalosporins contained non-mosaic PBP 2 sequences, of which PBP 2 pattern XIII was most common (28/46). All isolates with reduced susceptibility to cephalosporins also had mtrR and porB mutations. Two susceptible isolates had the PBP 2 pattern XIV and an incomplete MtrR protein, which was a new mutation. Isolates with identical PBP 2 patterns comprised multiple NG-MAST sequence types.Conclusions: Reduced susceptibility of N. gonorrhoeae to ceftriaxone and cefixime was associated with diverse penA mutations, particularly PBP 2 pattern XIII containing an Ala-501-->Val substitution, together with mtrR and porB mutations. The existence of only one strain having the mosaic penA sequence indicated that ceftriaxone and cefixime resistance in Korea is mostly not associated with a mosaic penA sequence. Highly heterogeneous NG-MAST sequence types excluded the clonal expansion of a particular subtype. [ABSTRACT FROM AUTHOR]

Purpose: The study purpose was to prospectively determine the accuracy of contrast-enhanced CT in diagnosing fatty liver using same-day biopsy as the reference standard.Materials and Methods: One hundred seventy-nine potential living liver donors underwent unenhanced and portal-phase contrast-enhanced hepatic CT and subsequent liver biopsy on the same day. Attenuation difference between the liver and the spleen on unenhanced (( pre ) L-S) and contrast-enhanced (( post ) L-S) images and blood-subtracted hepatic attenuation on contrast-enhanced images (( post ) L-B), calculated by [L - 0.3 x (0.75 x P + 0.25 x A)]/0.7 where L, P and A represent the attenuation of the liver, main portal vein and abdominal aorta, respectively, were obtained. The accuracy of these indices in diagnosing fatty liver according to various threshold levels, 5%-30% histological steatosis in increments of 5%, was compared using ROC analysis.Results: The area under the ROC curve for ( pre ) L-S, ( post ) L-S and ( post ) L-B was 0.663-0.918, 0.712-0.847 and 0.821-0.923, respectively, depending on the threshold levels of hepatic steatosis. The accuracy of ( pre ) L-S and ( post ) L-S did not differ (P >or= 0.054), despite a trend towards a lower accuracy with ( post ) L-S. ( post ) L-B yielded higher accuracy than ( pre ) L-S at threshold levels of 5% and 10% (P or= 0.144).Conclusion: Portal-phase contrast-enhanced CT has a similar, or even greater, accuracy than unenhanced CT in diagnosing fatty liver. [ABSTRACT FROM AUTHOR]

Introduction: A 25-year-old male underwent allogenic peripheral blood stem cell transplantation and developed sclerodermoid chronic graft versus host disease. He complained of limitation of motion of major joints and some difficulties with activities of daily living (ADL) performances.Discussion: He had been treated with physical and occupational therapies. After the rehabilitative managements, range of motion and ADL performances improved slightly.Conclusion: Active and continuous multimodal rehabilitative treatment would be helpful in managing contracture and functional impairment and preventing the progression of the disease. [ABSTRACT FROM AUTHOR]

Physiologic and physical differences between youth and mature adult athletes make children more vulnerable to injury. Providing youth athletes and their parents with information regarding risk factors, prevention guidelines, and more may help reduce the incidence of overuse injuries. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) is the abnormal development of bone within soft tissue. It is frequently encountered after traumatic brain injury or spinal cord injury, rather than lower motoneuron disease. It has been reported as a rare complication in Guillain-Barré syndrome (GBS). We present the case of a 31-year-old woman who suffered from pain and swelling with limitation of the passive range of motion on right hip joint, and who had been diagnosed with GBS about 1 year previously. She was wheelchair-bound and had incomplete tetraplegia with flaccidity. She was diagnosed as HO based on the radiologic imaging study. She did not reveal any encephalopathy-related symptoms or signs, and hypercalcemia, and/or related metabolic derangement during 1.5-year follow-up period. Owing to the paucity of other causative factors, we presumed that the long-time hypomobility, even though not accompanied by hypercalcemia, played a major role for the development of HO. Early active rehabilitative management was initiated. The outcome is not promising because of her long-standing paralyzed state; however, it was possible to prevent the aggravation of HO. Copyright © 2008 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation [ABSTRACT FROM AUTHOR]

Background: Displacement is an important risk factor for nonunion of scaphoid wrist fractures. We compared computed tomography with radiographs with regard to their ability to detect displacement.Methods: Six blinded observers rated thirty scaphoid fractures (ten displaced and twenty nondisplaced) with use of radiographs and computed tomography. The radiographs were evaluated separately from the computed tomography scans and then, in a third evaluation, the two imaging studies were reviewed simultaneously. The evaluations were repeated four weeks later. Observers were asked to evaluate specific measures of fracture displacement and then to judge the fracture as being displaced or nondisplaced.Results: Intraobserver reliability was better for computed tomography alone and the combination of radiographs and computed tomography than it was for radiographs alone (kappa values, 0.65, 0.63, and 0.54, respectively; all p<0.001). The interobserver reliability was also better for computed tomography alone and the combination of radiographs and computed tomography than it was for radiographs alone (kappa values, 0.43, 0.48, and 0.27, respectively; all p<0.001). The average sensitivity was 75% for radiographs alone, 72% for computed tomography alone, and 80% for both; the average specificity was 64%, 80%, and 73%, respectively; the average accuracy was 68%, 77%, and 75%, respectively. The positive predictive values (assuming a 5% prevalence of fracture displacement) were low (0.10, 0.13, and 0.16) and the negative predictive values were high (0.97, 0.98, and 0.99) for the radiographs, computed tomography, and combined modality.Conclusions: Computed tomography improves the reliability of detecting scaphoid fracture displacement but has a more limited effect on accuracy, which remains <80%. The utility of computed tomography scans for diagnosing scaphoid fracture displacement is affected by the low prevalence of fracture displacement. This study suggests that computed tomography scans are useful for ruling out displacement but not for diagnosing it. We recommend that all scaphoid fractures be evaluated with computed tomography in order to rule out displacement. [ABSTRACT FROM AUTHOR]

Background: To identify novel HLA-A*2402-restricted human cytomegalovirus (HCMV) immediate early-1 (IE-1) epitopes for adoptive immunotherapy, we explored 120 overlapping 15-amino acid spanning IE-1.Methods: These peptides were screened by measuring the frequency of polyclonal CD8+ T cells producing intracellular interferon-gamma (IFN-gamma) using flow cytometry and the epitopes were validated with a HCMV-infected target Cr release cytotoxicity assay.Results: Initial screening was performed with 12 mini-pools of 10 consecutive peptides made from 120 overlapping peptides15-amino acids in length that spanned IE-1. When peripheral blood mononuclear cells (PBMCs) from HLA-A*2402 HCMV-seropositive donors were sensitized with each of the 12 mini-pools, mini-pools 1 and 2 induced the highest frequency of CD8+ cytotoxic T lymphocytes (CTLs) producing IFN-gamma. When PBMCs were stimulated with each of the twenty peptides belonging to mini-pools 1 and 2, peptides IE-11-15MESSAKRKMDPDNPD and IE-15-19AKRKMDPDNPDEGPS induced the greatest quantities of IFN-gamma production and cytotoxicity of HLA-matched HCMV-infected fibroblasts. To determine the exact HLA-A*2402-restricted epitopes within the two IE-1 proteins, we synthesized a total of twenty-one overlapping 9- or 10 amino acid peptides spanning IE-11-15 and IE-15-19. Peptide IE-13-12SSAKRKMDPD induced the greatest quantities of IFN-gamma production and target cell killing by CD8+ CTLs.Conclusion: HCMV IE-13-12SSAKRKMDPD is a HLA-A*2402-restricted HCMV IE-1 epitope that can serve as a common target for CD8+ HCMV-specific CTLs. [ABSTRACT FROM AUTHOR]