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The status of the large grain niobium cavity R&D in Asia and the future scope are presented. Recently KEK has received CBMM and NingXia large grain niobium sheets through collaborations. KEK has fabricated 1.3 GHz single cell cavities using these materials and measured the cavity performance. Those results are presented in this paper.

In this paper, we examine numerically and experimentally the linear beam optics distortion in the storage ring of the Pohang Light Source (PLS), and the correction of optics using a number of quadrupole magnets installed in the storage ring. The measured orbit‐response matrices were fitted to the model‐response matrices to obtain β and dispersion functions in storage ring. By readjusting currents of quadrupole‐magnet power supplies, optics parameters were successfully restored to the values very close to the design ones. After the optics correction, it is expected that the performance of the storage ring is better than the present one.

We report on the recent experimental results on the fast-ion instability at the 2.5 GeV Pohang Light Source (PLS). In order to enhance the fast-ion instability in the PLS, we inserted helium gas to the storage ring in order to increase the vacuum pressure. With the gaps in the bunch train which is large enough to avoid multiturn ion trapping, we observed increase of a factor of 3-4 in the vertical beam sizes for the increased vacuum pressure up to 40 nTorr. The instability growth rate is obtained as a function of vacuum pressure and is also compared with the simulation results.

The PLS has provided 2.5 GeV electron beam to users of beam lines since Jan. 2000. During Jan. 2000 to Oct. 2002, 2 GeV electron beam was injected from the linac to the storage ring and the storage ring had used energy ramping process to increase the beam energy to 2.5 GeV. Instead of energy ramping process, we have used the 2.5 GeV full energy injection from the linac to the storage ring since Oct. 2002. We present the activities on the stability and reliability of the linac for 2.5 GeV operation, stabilities of injection kicker and septum magnets in the storage ring, orbit correction of COD due to leakage field of the septum magnet, and a DC bump for beam injection. Orbit stabilities and global orbit correction on the operation of 2.5 GeV full energy injection are also presented

Pohang Accelerator Laboratory(PAL) is working on a X‐ray self‐amplified spontaneous emission (SASE) FEL which will be driven by the upgraded injector linac. The preliminary idea is to upgrade the existing 2.5GeV injector linac to 3.0 GeV electron energy and use it as a driver for X‐ray SASE FEL. It also features utilization of the recent in vacuum undulator technology for shorter radiation wavelength . And the 3rd harmonic enhancement is considered for a possible option. In this report, the preliminary conceptual designs of the X‐ray SASE FEL at PAL including above features will be described.

AIMS: The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury. METHODS: We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks. RESULTS: All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period. CONCLUSION: Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease.

The purpose of this study was to investigate the dietary taurine intake and serum taurine levels of women on Jeju Island in Korea. Sixty six married women aged 43.5 +/- 7.1 volunteered for this study: 34 from the city area and 32 from two fishing-farming areas. Diet samples were collected from the participants; the samples included three meals (breakfast, lunch and supper), including snacks, drinks and whatever else the participants had eaten for 24 hours. Taurine levels in the diet and serum were determined as the dabsyl derivative by HPLC with a Rf-detector. The intake of taurine ranged from 8.4 to 767.6 mg/day and its mean value was 163.9 +/- 150.2 mg/day (mean +/- SD). There was a significant difference between the two groups: 114.9 +/- 78.7 for the women from the city area and 215.9 +/- 187.9 mg/day for the women from the fishing-farming areas (p0.001). The taurine intake of the total diet, including all snacks and drinks, was 2300 +/- 584 g/day for the city area and 2342 +/- 528 g/day for the fishing-farming areas. The daily protein intake was 58.8 +/- 16.4 g for the women of the city area and 65.5 +/- 17.1 g for the women of the fishing-farming areas. There was a significant correlation between the intake of fish/shellfish and taurine (p=0.001) while there was no correlation between the intake of protein and taurine (p=0.057). The taurine levels in serum ranged from 68.6 to 261.6 micromol/L and the mean value was 169.7 +/- 41.5 micromol/L. There was no significant difference between the women from the city area and the women from the fishing-farming areas in serum taurine levels. The correlations of serum taurine levels with serum retinol levels (p=0.016) and alpha-tocopherol (p=0.014) levels were significant. These results suggest that taurine intake is dependent on the fish/shellfish intake and that taurine may play an important role in the retention of antioxidative nutrients.

Proposes efficient postprocessing algorithms for error correction in handwritten Hangul (Korean script) address and human name recognition. As the load on the character recognizer for the recognition of the administrative district part in addresses was reduced by restricting the candidate characters to be matched based on a hierarchical address lexicon, the processing speed and recognition rate were greatly improved. Also, the misrecognition results from the character recognizer were corrected by using efficient postprocessing algorithms based on backtracking. For the recognition of the human name part, misrecognition of human names could be effectively corrected by combining the a priori probability and the confusion probability of each character making up the human names. >

Optical diagnostics are performed in concert with numerical simulations to characterize a new trapped- vortex combustor (TVC) for gas turbine engines. Variable parameters include the fuel composition, inlet pressure, inlet pressure drop, inlet temperature, and fuel-injection scheme. A number of experimental techniques are employed, such as high-speed digital imaging, coherent-structure velocimetry (CSV), particle-image velocimetry (PIV), and planar laser- induced fluorescence (PLIF) of hydroxyl (OH). The experimental data compare well with results from a computational fluid dynamics code (CFD) with chemistry, and are used to understand the flow pattern and flame location within the combustor. We discuss the utility of advanced diagnostics and simulations during the design and testing phase of combustor development.

Ota's naevus is among the dermal melanocytoses that show a distinct pattern involving skin innervated by the trigeminal nerve. Most cases present at birth or manifest clinically in early childhood. Cases of acquired lesions in adult onset have been reported rarely. We present two cases of late onset Ota's naevus which were confirmed by skin biopsies. Both patients underwent Q-switched alexandrite laser treatment with a dose of 8.0 J/cm2 given four or five times at 6 weekly intervals and showed some improvement.

The purpose of this study was to investigate whether serum concentration and urinary excretion of taurine are influenced by marginal taurine intake. Twenty one male patients (75 to 95 years old), suffering from coronary heart disease, multiple cerebral infarction, cancer, subdural hematoma or respiratory failure were grouped according to duration of tube feeding (group one, 5.9 +/- 2.9; group two, 14.8 +/- 2.3; group three 48.0 +/- 22.7, mean +/- SD, months). The mean intake of taurine was 347.0 +/- 25.6, 339.8 +/- 25.6 and 337.1 +/- 259 micromol/day (mean +/- SEM) in group one, two and three, respectively. The fasting serum taurine levels were 106.5 +/- 9.6, 95.0 +/- 9.9 and 56.8 +/- 11.0 micromol/L (mean +/- SEM) in group one, two and three, respectively. Taurine level in group three patients was significantly lower than that of group one and two (p0.05). The twenty-four hour urinary taurine excretion was 776.1 +/- 176.7, 782.4 +/- 245.3 and 388.3 +/- 169.3 micromol/day (mean +/- SEM) in group one, two and three, respectively. These results suggest that marginal taurine intake in patients receiving long term tube feeding could result in taurine deficiency.

Rare gas microplasmas confined in one dimension to ; 400 torr is introduced to the channel. The requirement for Penning gas mixtures in the narrowest channel appears to be associated with an accelerated electron loss rate.

Neuroblastoma (NB) is the most common extracranial neoplasm in children. In NB, loss of p53 function is largely due to cytoplasmic sequestration rather than mutation. Ubiquitin-conjugating enzyme E2 N (UBE2N), also known as Ubc13, is an E2 ubiquitin-conjugating enzyme that promotes formation of monomeric p53 that results in its cytoplasmic translocation and subsequent loss of function. Therefore, inhibition of UBE2N may reactivate p53 by promoting its nuclear accumulation. Here, we show that NSC697923, a novel UBE2N inhibitor, exhibits potent cytotoxicity in a panel of NB cell lines evidenced by its ability to induce apoptosis. In p53 wild-type NB cells, NSC697923 induced nuclear accumulation of p53, which led to its increased transcriptional activity and tumor suppressor function. Interestingly, in p53 mutant NB cells, NSC697923 induced cell death by activating JNK pathway. This effect was reversible by blocking JNK activity with its selective inhibitor, SP600125. More importantly, NSC697923 impeded cell growth of chemoresistant LA-N-6 NB cell line in a manner greater than conventional chemotherapy drugs doxorubicin and etoposide. NSC697923 also revealed in vivo antitumor efficacy in NB orthotopic xenografts. Taken together, our results suggest that UBE2N is a potential therapeutic target in NB and provide a basis for the rational use of UBE2N inhibitors like NSC697923 as a novel treatment option for NB patients.

Hepatitis B and C virus infection prevalence was investigated in the Island of Jeju (formerly Cheju), the Republic of Korea, by means of a small-scale sero-epidemiological survey in 2000. Adult women in the city of Jeju (the provincial capital) and two fishing-farming villages A and B were invited to offer venous blood samples for immunological examination for infection markers of two virus and serum biochemistry for liver function. In practice, 66 married women (33, 16 and 17 women from the city, Village A and Village B, respectively) volunteered. Sera were separated on site and were assayed for HBsAg, anti-HBs, anti-HBc, and anti-HCV positivities and liver function markers including AST, ALT and gamma-GTP. The serum assay showed that the prevalence of HbsAg+ or anti-HCV+ cases was low (5 and 2%, respectively), whereas that of anti-HBs+ and anti-HBc+ cases were high (71 and 62%) so that the over-all HBV positivity was 82%. There were essentially no urban-rural difference or age-dependent changes in the positivity. Comparison with the prevalence reported in literature shows that prevalence of HBsAg+ and anti-HCV+ is in general agreement with the values reported for the populations in general, but HBV+ prevalence might be somewhat higher than the levels reported for the general populations.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

In the past few years, the concept of a high intensity muon storage ring has been pursued as an option for the next generation neutrino source. To produce the high intensity muon beam needed for the successful operation of a neutrino source, on the order of 10^{20} muon decays per year, the phase space occupied by the muon beam must be significantly reduced before the beam is accelerated. The initial transverse emittance of the muon beam before acceleration is assumed to be 9π mm rad. Because of the time limitation imposed by the muon lifetime, the technique employed to accomplish the desired emittance reduction is ionization cooling. In this paper we present two ionization cooling lattice designs, which use solenoidal focusing elements and liquid hydrogen absorbers to reduce the muon beam phase space. We discuss the design concepts and engineering constraints for these lattices and present simulation results obtained using a detailed tracing code with a complete model of muon-matter interactions. The reduction in transverse emittance is approximately a factor of 5. This result is within a factor of 2 of the total cooling requirements for a successful neutrino factory design and within a factor of 1.4 of the requirements for the main cooling section specified in the conceptual design of this machine.

We have characterized full-length cDNAs encoding two isoforms of agriusin, cecropin D-like antibacterial peptide, present in the hemolymph of the immunized Agrius convolvuli larvae. The cloned cDNAs of agriusins 1 and 2 contain 331 and 329 bp, respectively. The nucleotide sequencing of cDNAs showed that they encode 62 amino acids, whose mature portion was deduced to consist of 38 amino acid residues with over 94% sequence identity. In the sequence homology search, mature agriusin 1 showed over 86 and 71% amino acid sequence homology with bactericidin 4 from Manduca sexta and cecropin D from Hyalophora cecropia, respectively. Since it was demonstrated from the deduced amino acid sequences that the C-terminal residues of agriusins are followed by a Gly residue, two types of synthetic agriusin 1 (syn-agriusin 1 amide and acid) were prepared to verify if natural agriusin 1 is C-terminally amidated. From acid-urea PAGE and reversed phase HPLC profiles to compare two synthetic peptides, we could confirm that the C-terminal amino acid residue of natural agriusin 1, like several cecropins so far identified, is amidated. Finally, our antibacterial assay performed with two syn-agriusins 1 revealed that there is little difference between antibacterial activities of both peptides against Gram-positive and Gram-negative bacteria.

Arsenic trioxide (As2O3) has been shown to inhibit the proliferation of hematologic malignant cells. Previously, we reported that As2O3 had an antitumoral effect in head and neck cancer. Here, we investigated the induction of apoptosis and its mechanism in PCI-1 head and neck squamous carcinoma cells, after treatment with As2O3. Treatment with 2 microM of As2O3 caused apoptosis in PCI-1 cells following 3 days of exposure, which was detected by the annexin V-PI and DAPI staining methods. The cell death population was markedly increased, being 88% larger than the As2O3-untreated control cells. To address the mechanism of apoptosis, a Western blot assay was performed, showing that Bax was up-regulated without a change in Bcl-2. Activation of caspase-9 during As2O3-induced apoptosis was substantiated by monitoring the proteolysis of the caspase-9, which was associated with an increase of Apaf-1 and cytochrome c protein. PCI-1 cells rapidly changed the mitochondria membrane potential (DeltaPsim) after addition of As2O3. Furthermore, activation of caspase-3 was demonstrated by monitoring the proteolysis of the caspase-3 and by measuring caspase-3 activity with a fluorogenic substrate, which was associated with the cleavage of poly(ADP-ribose) polymerase. To examine the in vivo effect of As2O3, C3H mouse inoculated with syngenic SCC7 cells was treated by intratumoral injection of As2O3 (300 microg) every day, demonstrating that tumor mass was dramatically reduced on day 4, and revealed induction of apoptosis by TUNEL assay. These results suggest that apoptosis of PCI-1 cells by As2O3 is induced by activation of caspase-3 via cytochrome c, caspase-9 and Apaf-1 complex.

The eight mammalian Smad proteins mediate cellular signaling from members of the transforming growth factor-beta (TGF-beta), bone morphogenetic protein (BMP), and activin families. Smads 1, 5, and 8 transmit signals from BMPs, while Smads 2 and 3 transmit signals from TGF-betas and activin. Smad 4 is a common mediator of both pathways, while Smads 6 and 7 inhibit signaling. Signal transduction involves translocation of Smad complexes to the nucleus and subsequent gene activation. Little is known about the expression of endogenous Smad proteins during development. We identified commercially available Smad antibodies that specifically recognize a unique Smad protein and are suitable for immunohistochemistry. Here we compare the localization of Smads 1, 2, 3, 4, 5, and 6 in tissues of the 15-day gestation mouse embryo. Immunoreactive Smad proteins are seen in many tissues with differences in the localization being dependent upon the cell type. All tissues express Smad 4 and at least one each of the BMP-specific and TGF-beta-specific Smads, while expression of Smad 6 is more restricted. Differences are observed in the nuclear versus cytoplasmic localization among the Smads in different cell types or tissues, suggesting selective activation of Smads during this stage of development.

Lung cancer is the leading cause of cancer-related death worldwide and in the United States surpassing breast, prostate, and colon cancer. Treatment of this disease over the past 2 decades has advanced incrementally as survival rates have improved only slightly. Alternate approaches to this deadly disease include an emphasis on prevention such as smoking cessation. Chemoprevention has introduced a new arena of treatment options for early intervention in lung carcinogenesis. The use of molecularly targeted therapeutic and biologic agents constitutes novel strategies for lung cancer prevention in the new millennium.

EB1089, a novel 1,25-dihydroxyvitamin D3 analogue, has been known to have potent antiproliferative properties in a variety of malignant cells both in vitro and in vivo. In the present study, we analysed the effect of EB1089 on NCI-H929 human myeloma cells. EB1089 inhibited cell growth of NCI-H929 and efficiently induced the G1 phase arrest of the cell cycle in a dose-dependent manner. We could also detect apoptosis in NCI-H929 cells exposed to EB1089 (1 x 10-7 M for 72 h) using the sub-G1 group of the cell cycle by FACS and annexin V binding assays. Induction of apoptosis by EB1089 was associated with down-regulation of the Bcl-2 protein without change of the Bax protein. Regarding caspase activity, which plays a crucial role in apoptosis, EB1089-treated NCI-H929 cells revealed an increased activity of caspase 3 protease accompanied by degradation of the PARP protein in a dose- and time-dependent manner. In addition, EB1089 caused the down-regulation of p44 extracellular signal-related kinase (ERK) activity and up-regulation of the p38 kinase activity during apoptosis of NCI-H929 cells. These results suggest that EB1089 inhibits growth of NCI-H929 cells via G1 cell cycle arrest as well as apoptosis by activating p38 kinase and suppressing ERK activity.

We investigated the in vitro effect of As2O3 on proliferation, cell cycle regulation, and apoptosis in human myeloma cell lines. As2O3 significantly inhibited the proliferation of all of eight myeloma cell lines examined in a dose-dependent manner with IC50 of approximately 1-2 microM. DNA flow cytometric analysis indicated that As2O3 (2 microM) induced a G1 and/or a G2-M phase arrest in these cell lines. To address the mechanism of the antiproliferative effect of As2O3, we examined the effect of As2O3 on cell cycle-related proteins in MC/CAR cells in which both G1 and G2-M phases were arrested. Western blot analysis demonstrated that treatment with As2O3 (2 microM) for 72 h did not change the steady-state levels of CDK2, CDK4, cyclin D1, cyclin E, and cyclin B1 but decreased the levels of CDK6, cdc2, and cyclin A. The mRNA and protein levels of CDKI, p21 were increased by treatment with As2O3, but those of p27 were not. In addition, As2O3 markedly enhanced the binding of p21 with CDK6, cdc2, cyclin E, and cyclin A compared with untreated control cells. Furthermore, the activity of CDK6-associated kinase was reduced in association with hypophosphorylation of Rb protein. The activity of cdc2-associated kinase was decreased, which was accompanied by the up-regulation of cdc2 phosphorylation (cdc2-Tyr15 phosphorylation) resulting from reduction of cdc25B and cdc25C phosphatases. As2O3 also induced apoptosis in MC/CAR cells as evidenced by flow cytometric detection of sub-G1 DNA content and annexin V binding assay. This apoptotic process was associated with down-regulation of Bcl-2, loss of mitochondrial transmembrane potential (delta psi(m)), and an increase of caspase-3 activity. These results suggest that As2O3 inhibits the proliferation of myeloma cells, especially MC/CAR cells, via cell cycle arrest in association with induction of p21 and apoptosis.

An inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, lovastatin, induces growth arrest and cell death in a wide variety of malignant cells in vitro. We analyzed the effect of lovastatin on myeloid leukemic cell lines. Lovastatin significantly inhibited the proliferation of 7 cell lines among 11 myeloid leukemic cell lines in a dose-dependent manner. In order to address the mechanism of antileukemic effect of lovastatin, cell cycle analysis was attempted in HL-60 cells, showing that lovastatin induced G1 arrest in HL-60 cells following 72 h of drug exposure (1.5 microM, 5 microM and 10 microM) in a dose-dependent manner. Analysis of G1 regulatory proteins demonstrated that the protein levels of cyclin-dependent kinase (CDK) 2, CDK4, CDK6 and cyclin E were decreased after treatment with lovastatin (10 microM) in a time-dependent manner, but not cyclin D1. In addition, lovastatin increased the protein level of the cyclin-dependent kinase inhibitor (CDKI), p27, and markedly enhanced the binding of p27 with CDK2 and CDK4 more than CDK6 after 24 h exposure. At higher doses of lovastatin (50 mM, 100 mM, 200 mM), a significant apoptosis was observed as evidenced by FACS analysis with annexin V staining, which was associated with downregulation of Bcl-2 protein. These results suggest that lovastatin inhibits the proliferation of myeloid leukemic cells via G1 arrest in association with p27 induction and is an effective inducer of apoptosis in HL-60 cells.

Progression of cell cycle in eukaryotes is regulated by a series of the cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs). It has been shown that 1,25(OH)2D3 is able to arrest cell cycle at G1 phase in malignant cells including HL-60 cells. EB1089 is a novel 1,25(OH)2D3 analog that has more potent antileukemic properties with reduced hypercalcemic effect in vitro and in vivo than 1,25(OH)2D3. In the present study, we examined the effect of EB1089 on HL-60 cells at the protein levels of several G1 regulatory proteins. Exposure of HL-60 cells to EB1089 (1x10-8 M) for 3 days showed the G1 block by FACS analysis. The level of p21 was markedly induced in HL-60 cells treated with EB1089 at 24 h, and p27 were progressively increased in a time-dependent manner. The expressions of CDK2 and CDK6 were down-regulated during G1 block of HL-60 cells, and CDK4 is progressively elevated. In addition, level of cyclin D1 was increased in a time-dependent manner, however, no change of cyclin E was noted through the G1 to S traverse. Immunoprecipitation study demonstrated that p27 did not bind to CDK2, CDK4 and CDK6 in EB1089-treated HL-60 cell extracts. In contrast, complexes immunoprecipitated from EB1089-treated HL-60 cells with antibodies CDK2 and CDK6 contained higher amounts of immunodetectable p21 protein compared to untreated HL-60 cells, whereas no detectable change was noted with anti-CDK4 antibody. Furthermore, the kinase activities of CDK2 and CDK6 were decreased while little change was observed in CDK4 activity. These data indicated that p21 protein is a strong candidate for the control of G1 progression in EB1089-treated HL-60 cells, and its major target molecules are CDK2 and CDK6.

To evaluate the findings of tetralogy of Fallot in various fetal sonographic views.We reviewed the fetal sonograms and medical records of 20 fetuses with prenatal diagnosis of tetralogy of Fallot. We analyzed the indications for targeted sonography, the abnormalities seen in various sonographic views, the postnatal echocardiographic and angiographic findings and autopsy findings.The most common indication for targeted sonography was an abnormal (n = 12) or inadequate (n = 3) finding on sonographic screening in which the abnormality was most frequently found on the three-vessel view (n = 9). The key pathological features of tetralogy of Fallot were uniformly demonstrated in the ventricular outflow tract, three-vessel and short-axis views. The ductus arteriosus was small in 70% of cases and not identifiable in the remaining fetuses. In three of six fetuses with no identifiable ductus, the ductus was shown to be absent at autopsy. The direction of ductal flow was variable.The key features of tetralogy of Fallot were always demonstrable in the ventricular outflow tract, three-vessel and short-axis views. The most common reason for referral was the abnormal three-vessel view.

A case of congenital epulis in a triple X infant, whose intra-oral mass was first detected on a 33-week prenatal ultrasound, is described. Two previous ultrasound studies performed at 21 and 28 weeks' gestation showed normal facial anatomy, suggesting accelerated tumour growth during the third trimester. Genetic amniocentesis also showed the infant to possess a 47, XXX karyotype.

The urokinase-type plasminogen activator (uPA) and uPA receptor (UPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. sc. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established so U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.

With these results we report the following: Taurine levels in human milk decreased slightly during the early lactation period. The concentration of taurine (406 +/- 174 nmol/ml) in colostrum was significantly higher than that (335 +/- 115 nmol/ml) in mature milk. Selenium content of human milk also decreased slightly during the early lactation period. The content of selenium (28.6 +/- 19.6 ng/ml) in colostrum was significantly higher than that (1 5.1 +/- 5.9 ng/ml) in mature milk. A correlation was not found between the taurine and selenium content of human milk. The intake of taurine and selenium by breast-fed infants progressively increased with days postpartum. These results were due to the significant increase in milk intake by infants. It is suggested that the taurine and selenium levels in colostrum are more concentrated than those in mature milk. However, the absolute intake of taurine and selenium by infants are higher in mature milk.

Plastids in lipophilic glandular trichomes of chemically fixed (CF) and high pressure cryofixed-cryosubstituted (HPC-CS) bracteal tissues of Cannabis were examined by transmission electron microscopy. In CF preparations, plastids in disc cells prior to secretory cavity formation possessed several lobed and dilated thylakoid-like features. In glands with secretory cavities, thylakoid-like features aggregated to form reticulate bodies that distended regions of the elongated plastids. Electron-gray inclusions evident on the plastid surface appeared continuous with the reticulate body. Inclusions of similar electron density also appeared in the cell cytoplasm, along the plasma membrane, between the plasma membrane and cell wall facing the cavity, and in the secretory cavity in both CF and HPC-CS preparations. The bilayer structure of membranes of the plastid envelope was evident in HPC-CS but not in CF preparations. In HPC-CS preparations, secretions were evident on the plastid surface and were continuous with those in the plastid through pores in the envelope. This study supports an interpretation that these specialized plastids, lipoplasts, synthesize secretions that are transported through the plasma membrane and cell wall to subsequently accumulate in the secretory cavity.

The three-vessel view is a transverse view of the fetal upper mediastinum is as simple to obtain as the four-chamber view. It demonstrates the main pulmonary artery, ascending aorta and superior vena cava in cross- or oblique sections. The purposes of this study were to describe the normal anatomy of the three-vessel view and to analyze what anatomical changes would occur in this view when there are lesions of the ventricular outflow tracts and/or great arteries. Sonograms of 29 fetuses with lesions involving the ventricular outflow tracts and/or great arteries were reviewed. Three-vessel views were evaluated in terms of vessel size, number, arrangement and alignment. Twenty-eight of 29 fetuses showed an abnormal three-vessel view that included abnormal vessel size (n = 12), abnormal alignment (n = 8), abnormal arrangement (n = 7) and abnormal vessel number (n = 3). The vessel size was abnormal in obstructive lesions of the right (n = 4) or the left (n = 8) side of the heart. An abnormal alignment was seen in tetralogy of Fallot (n = 6) and double-outlet right ventricle (n = 2) that showed anterior displacement of the aorta. An abnormal arrangement was seen in complete (n = 4) and corrected (n = 1) transposition, double-outlet right ventricle (n = 1) and pulmonary atresia with ventricular septal defect (n = 1). Only two vessels were seen in truncus arteriosus (n = 1). Four vessels were seen in persistent left superior vena cava (n = 2). A fetus with pulmonary atresia and intact ventricular septum showed a normal three-vessel view. In conclusion, most of the lesions involving the ventricular outflow tracts and/or great arteries showed an abnormal three-vessel view.

The seco-steroid 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) induces differentiation and inhibits clonal proliferation of HL-60 cells. We analyzed the effect of a novel vitamin D3 analog, EB1089, on normal myeloid and leukemic cells as well as CD34+ cells. EB1089 showed an extraordinary inhibition of clonal growth of HL-60 cells (ED50 = 5 x 10(-11) M) and AML blast cells (ED50 = 9 x 10(-10) M) compared to 1,25(OH)2D3 without suppression of growth of normal human bone marrow CFU-GM. The CD34+ cells from acute myeloid leukemia (AML) blasts were inhibited in a dose-dependent fashion by 1,25(OH)2D3 with an ED50 of 1.2 x 10(-9) M; and even more strikingly, 10(-10) M of EB1089 inhibited all clonal growth of human CD34+ leukemic colony-forming cells. In contrast, both EB1089 and 1,25(OH)2D3 (10(-8) M) showed little or only mild inhibition of CD34+ clongenic hematopoietic cells from normal human peripheral blood (PB); and in liquid culture, EB1089 stimulated the proliferation of normal human CD34+ cells about 2.5 times as compared to control cultures. In order to evaluate the potential use of EB1089 for purging leukemic cells from normal CD34+ progenitor cells for PB stem cell transplantation (PBSCT), normal human PB mononuclear cells (PBMNC) were contaminated with HL-60 cells, and then CD34+ cells purified and treated with EB1089. We found that CD34+ purification and EB1089 purging was able to eliminate approximately 100% of HL-60 leukemic cells with no toxicity to normal CD34+ hematopoietic progenitor cells. These data suggested that purification of CD34+ cells and ex vivo treatment with EB1089 might provide an effective therapeutic approach for PBSCT.

With the use of microsurgery, we have developed a method of measuring hemodynamic parameters in a rat not possible with previous technology. Three groups of rats were studied: a chemically induced pulmonary hypertensive group (PH); a chemically induced pulmonary hypertensive group treated with single lung transplantation (LT); and an untreated, control group (C). Cardiac output, heart rate, and pulmonary vascular resistance were then calculated in each group from data obtained by 1 mm high fidelity micromanometers and an ultrasonic flow probe. The results show that the data collected from the rodent model are reproducible within each group, and data quality is comparable to large animal models. With this new method, data can be collected in a small animal model at a fraction of the time and cost of large animal studies. Additionally, the complications of graft rejection in large animal studies are eliminated in an isogenic rodent model.

i. Taurine concentrations of human milk of nonvegetarians and lacto-ovovegetarians decreased significantly during the course of lactation. Taurine concentrations in lacto-ovovegetarians after 90 days postpartum were lower than those of nonvegetarians. Taurine concentrations of human milk by 150 days postpartum were: nonvegetarian 248-434 nmol/ml (31.0-54.4 mg/L); lacto-ovovegetarian 153-418 nmol/ml (19.1-52.3 mg/L). ii. Taurine intakes in infants of lacto-ovovegetarians decreased significantly during lactation, unlike from the pattern in infants of nonvegetarians. Taurine intakes in infants of lacto-ovovegetarians at 90, 120 and 150 days postpartum were lower, compared with those in nonvegetarians. Taurine intakes in infants by 150 days postpartum were: Infants of nonvegetarians 169-229 mumol/day (21.1-28.6 mg/day); Infants of lacto-ovovegetarians 106-210 mumol/day (21.1-28.6 mg/day). iii. This study showed that the taurine concentration in human milk and the taurine intake of infants were different during lactation between nonvegetarians and lacto-ovovegetarians, and that the intake per kg body weight decreased during lactation. Results suggest that the differences observed might be due to the effect of consumption of different types of food.

By focused ion beam milling, we fabricated near-IR reflective metamaterials consisting of nano-aperture arrays. Optimum parameters of ion beam current and accelerating voltage in the fabrication process are obtained. Nano-apertures constituting reflective metamaterial are successfully milled, and possess a reflective resonance in the near-IR spectral range. With a double-split-ring resonator structure for the nano-aperture, the intensity reflection at resonance is rendered polarization dependent. It is found that the point group symmetry of the nano-aperture array determines the amount of anisotropy in the intensity reflection. Finite-difference time-domain simulation was adopted to identify details of nano-aperture metastructures transferred from nano-aperture patterns by the focused ion beam milling.

Background: Circulating tumor cells (CTC) associated with solid tumors are being studied for their diagnostic and prognostic value. In patients with metastatic tumors, CTC presence in the blood has been putatively associated with short survival. Since blood collection is relatively non-invasive, CTC molecular analysis opens up the possibility of monitoring genotypic changes during cancer treatments. Unfortunately, CTCs are not present in large numbers, often at rates as low as one cell per 106-107 leukocytes. Thus, to perform genotypic biomarker analysis on CTCs, methodologies must be developed to using highly specific and sensitive technologies and an enrichment step to increase analytes to detectable levels. Methods: We developed a methodology for detecting mutations in multiple oncogenes and chemotherapy resistance genes in non-small cell lung cancer (NSCLC) CTC specimens using high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) single nucleotide polymorphism (SNP) analysis (MASSarray; Sequenom, Inc.) to determine cancer-associated genetic mutations in lung cancer specimens. This system allows for up to 10 different somatic mutations to be assayed per well in a 384-well format; requires very little DNA; can be used with whole genome amplified (WGA) DNA; and is sensitive enough to use with small samples such as core needle biopsies (CNB), fine needle aspirates (FNA), and CTCs. We developed a lung cancer assay panel of 13 genes/135 mutations (including AKT1, BRAF, CTNNB1, EGFR, ERBB2, KRAS, MEK1, NRAS, PIK3CA, PIK3R1,PTEN, and STK11) to test for somatic mutations in genes representing multiple pathways known to be involved in lung cancer. All assays can detect a mutation in < 25% of a sample. Results: In the effort to analyze CTCs, we first analyzed 57 NSCLC cell lines with known mutations and confirmed known mutation status. Next, we successfully analyzed DNA from 90 frozen and matched FFPE NSCLC resected tissues. Analysis of unamplified and matched WGA cell line DNA quantity CNB and FNA equivalents gave the same mutational status results. Moving to CTC equivalents, we successfully analyzed cell line DNA and matched WGA DNA equivalents of 100–1000 cells with known EGFR L585R and KRAS G34A mutations and negative control DNA (negative for all assays). Next, WGA methodology for direct CTC cell lysate DNA amplification was developed using CTC cell number equivalents (3 – 200 cells) obtained from a typical clinical blood sample CTC preparation. Then, we directly compared unamplified and matched amplified CTC cell equivalents (50, 100, and 200 cells). Analysis of both unamplified and amplified CTC cell equivalents reported identical mutation status results. We have applied this methodology to spiked blood sample and clinical blood sample CTC fractions. Thus, we demonstrated that we are able to study mutations in multiple genes using small amount of DNA from CTC cell numbers in a high-throughput manner. Conclusion: We developed a robust method for accurately determine cancer-associated genetic mutations in NSCLC CTC cell number equivalent lysates using MALDI-TOF MS SNP analysis which can be applied to better understand the molecular characteristics of lung cancer during treatment and progression. As additional clinical NSCLC CTC samples are collected, we will continue applying this methodology to assess CTC mutation status as potential diagnostic and/or prognostic markers.

7053 Background: Patients (pts) with resected ES NSCLC are at risk for recurrence of disease and mortality but we do not have tools to predict which pts are at highest risk. Risk models have been p...

5520 Background: In EGFR over expressing cell lines, higher doses of erlotinib block downstream signaling more effectively (e.g., MAPK) than lower doses, despite a similar degree of EGFR phosphoryl...

7550 Background: BATTLE was a phase II trial that randomized 255 patients (pts) into 4 separate trials: erlotinib (E), erlotinib-bexarotene (E-B), vandetanib (V), and sorafenib (S). Treating elderl...

1506 Background: We have reported that a gene expression signature including DNMT3B canpredict OC development (dvlpt) in patients (pts) with oral preneoplasia (OPL). This led us to study OPL DNA methylation profiles. Methods: Gene expression profiles of 86 prospectively collected OPL with a median follow-up (fu) of 6.1 years (yrs), including 35 who developed OC, were used to compute a univariate Cox model for DNMT1, 3A and 3B. Methylated CpG island amplification method was used to study 12 OPL who developed (group A), and 12 OPL who did not develop (group B) OC, with a median fu of 2.2 yrs and 7.6 yrs respectively. DNA was SmaI/XmaI digested, amplified, labeled (each OPL of group A being compared to one OPL of group B), and hybridized on a chip covering 6,647 autosomal genes. Genes differentially methylated were defined by an absolute log2 ratio > 1, at least 2 probes showing the same effect, and an absolute minimal distance to the transcription starting site < 1kb. Their pattern of expression was analyze...

We have developed a chemosensitivity assay of human tumors growing on collagen-sponge-gel-supported histoculture. This assay is thus termed the Histoculture Drug Response Assay (HDRA). In the HDRA, the end points of [3H]thymidine incorporation measured by histological autoradiography and tetrazolium dye reduction were initially used and found to have good in vitro-in vivo correlations, including that determined in clinical trials. We have now developed glucose consumption as an endpoint in histoculture. We have monitored glucose consumption for 11 weeks with histocultured stomach cancer tissue that was obtained from a patient with stomach cancer metastatic to the lymph node. The histocultured lymph node specimens were treated with various concentrations of doxorubicin and cisplatinum. The glucose-consumption rate decreased with greater concentrations of both drugs. The results correlated with the thymidine labeling index. From these results, we conclude that the glucose-consumption-rate endpoint in histocultured cancer tissue is non-destructive, unlike the [3H]thymidine and tetrazolium dye end points, allowing serial determinations over extended periods in culture. Thus, the glucose consumption end point may enhance the development of optimal treatment doses and schedules. We also conclude that long-term histoculture drug response studies of metastatic stomach cancer are possible.

This report was done mid way through the study "A Demonstration-Cum-Research on the Reimbursement system and cost-effectiveness of Home Health Care Program in Korea". It focused on developing an estimation of early discharge day to home health care based on analysis medical records and on an analysis of medical expenses based on a detailed statement of treatment for inpatients who were hospitalized at S General Hospital in 1991. Two research methods were adopted for estimation of the early discharge day. One was micro-analysis from the medical records and the other was macro-analysis to clarify the estimated early discharge day to home health care for patients with four diseases judged from need assessment to be candidates for this type of program, namely patients with, Cesarean Section, Hypertension, Diabetes Mellitus, Chronic Obstructive Pulmonary Disease (COPD). Estimation of early discharge day to home health care were developed through many aspects of analysis of the signs and symptoms by disease in a micro-analysis in addition to a decrease in the amount of treatment, drugs, tests and changes in the test consistency, drug methods, and client's condition in the macro-analysis. Accordingly, an early discharge day for inpatients was finally estimated through the analysis of the client's conditions and treatment, drugs, tests, and nursing care activities that the patient received during hospitalization. From the research findings, the following summarized conclusions have drawn. First, for patients with Cesarean Sections, after assessing each items using the two analysis methods, the mean period of hospitalization was 8.8 days, but the mean period of hospitalization was estimated at 4.1 days if early discharge to home health care could be done. Second, for patients with Hypertension, the same method as for the patients with the Cesarean Sections was used and the result was reduction from a mean period of the hospitalization of 9.9 days to a mean period of the hospitalization of 5.2 days. Third, for patients with Diabetes Mellitus there was a decrease from a mean period of the hospitalization of 11.7 days to a mean period of hospitalization of 8.4 days if early discharge to home health care could be done. Fourth, for patients with Chronic Obstructive Pulmonary Disease, the mean period of the hospitalization was 14.3 days, but the mean period of the hospitalization could be 8.1 days if early discharge to home health care could be done.(ABSTRACT TRUNCATED AT 400 WORDS)

A metamaterial-liquid crystal cell structure is fabricated with the metamaterial as one of the liquid crystal alignment layers. Nano-sized double-split ring resonator in the metamaterial accommodates two distinct resonances in the near infrared regime. By adopting an azo-nematic liquid crystal in a twisted nematic liquid crystal cell structure, a photo-isomerization process is utilized to achieve an optical switching of light transmissions between two resonances. A single device of the metamaterial-liquid crystal cell structure has a potential application in the photonic switching in optical fiber telecommunications.