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Tooth development is regulated by reciprocal interactions between epithelial and mesenchymal cells. Several morphological studies suggest that growth factors secreted from these cells regulate tooth development. These growth factors induce undifferentiated cells in the tooth germ to differentiate into tooth-forming cells. Many growth factors are reportedly expressed in the developing tooth, but the key molecule underlying tooth root development is still unknown. There is a considerable amount of data on the expression and function of bone morphogenetic proteins (BMPs) during tooth development, but the relationship between BMPs and tooth root development has not been analyzed extensively. This prompted us to examine the expression patterns of BMP4 and BMP receptors (BMPRs) at the apical region of the tooth germ during mouse tooth root development. We found that BMP4 was strictly expressed in the apical mesenchyme, and that BMPRs were localized in Hertwig's epithelial root sheath (HERS). We also investigated the possible roles of BMP4 in HERS during the early stage of tooth root development. Our organ-culture results indicated that BMP4 regulates HERS formation via harmonious interactions with its own antagonist, noggin, by preventing elongation and maintaining cell proliferation. BMP4 may therefore be useful in various tissue-engineering applications as a regulator of tooth root formation.

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [11C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off-medication, two series of 15 trains of 5 Hz-frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (−4.9% and −6.5%, respectively) (P > 0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (−6.6%, P > 0.05 and −12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 ± 14.1 to 32.0 ± 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS. © 2007 Movement Disorder Society

Recent increases in the demand for mobile devices have stimulated the development of nonvolatile memory devices with high performance. In this Communication, we describe the fabrication of low-cost, high-performance, digital nonvolatile memory devices based on semiconducting polymers, poly(o-anthranilic acid) and poly(o-anthranilic acid-co-aniline). These memory devices have ground-breaking and novel current-voltage switching characteristics. The devices are switchable in a very low voltage range (which is much less than those of all other devices reported so far) with a very high ON/OFF current ratio (which is on the order of 10 5 ). The low critical voltages have the advantage for nonvolatile memory device applications of low operation voltages and hence low power consumption. With this very low power consumption, the devices demonstrate in air ambient to have very stable ON- and OFF-states without any degradation for a very long time (which has been confirmed up to one year so far) and to be repeatedly written, read and erased. Our study proposes that the ON/OFF switching of the devices is mainly governed by a filament mechanism. The high ON/OFF switching ratio and stability of these devices, as well as their repeatable writing, reading and erasing capability with low power consumption, opens up the possibility of the mass production of high performance digital nonvolatile polymer memory devices with low cost. Further, these devices promise to revolutionize microelectronics by providing extremely inexpensive, lightweight, and versatile components that can be printed onto plastics, glasses or metal foils.

Herein, wereport a method to control the adhesion and shape of MSCsusing monolayered CNT patterns. As a proof of concept, wepatterned various 1D nanostructures, including CNTs andNWs, on substrates, and MSCs were subsequently culturedand observed on the patterned substrates. In this work, self-assembled monolayer (SAM) patterns were first used todirect the assembly of single-walled CNTs (swCNTs) andmulti-walled CNTs (mwCNTs) on solid substrates. A self-limiting mechanism ensured the assembly of only a singlelayer of CNTs, without significant change of surface morphol-ogy. Importantly, the MSCs exhibited preferential growth onCNT patterns, and the cell culture results suggested that theCNT patterns did not have a harmful effect on the MSCs.Further, we demonstrated the growth of MSCs on swCNTpatterns between electrodes. These results clearly show thatCNT patterns have enormous potential as a new platform forbasic research and applications using stem cells.Figure 1 shows a schematic diagram depicting our experi-mental procedure for directed MSC growth. First, a non-polarSAM of 1-octadecanethiol (ODT) was patterned, while leav-ing some bare Au regions (Fig. 1A). SAM patterning on Aucan be achieved using dip-pen nanolithography (DPN)

Glucocorticoids (GCs) alter metabolism, synaptogenesis, apoptosis, neurogenesis, and dendritic morphology in the hippocampus. To better understand how glucocorticoids regulate these aspects of hippocampal biology, we studied gene expression patterns in the CA3 (Hippocampal pyramidal cell field CA3) and dentate gyrus (DG). Litter-matched Lewis inbred rats treated for 20 days with either 9.5 ㎎ per day sustained-release corticosterone or placebo pellets were compared with high-density oligonucleotide microarray analysis (Rat Neurobiology U34 Arrays, Affymetrix). In placebo-treated rats, 32 genes were expressed at greater levels in CA3 than DG, whereas 3 genes were expressed at great levels in DG than CA3. Regional differences were also apparent in corticosterone-induced changes in the hippocampal transcriptome. Six genes in CA3 and 41 genes in DG were differentially regulated by corticosterone. As per the glucocorticoid effects on gene transcription in the brain, forty three of these genes were upregulated, and 4 genes were downregulated. Genes differentially expressed in hippocampus included those for 13 neurotransmitter proteins, 5 ion channel related proteins, 4 transcription factors, 3 neurotrophic factors, 1 cytokine, 1 apoptosis related protein, and 5 genes involved in synaptogenesis. Interestingly, GCs can have suppressive effects on brain BDNF mRNA transcription, one of the neurotrophic factors. These results indicate the diversity of targets affected by chronic exposure to corticosterone and highlight important regional differences in hippocampal neurobiology.

The purpose of this study was to related energy consumption lifestyle habits of overweight Office worker in Korea. A total of 84 male office worker voluntarily participated in the study, and the participants underwent the meas- urements of energy consumption lifestyle habits and BMI. For groups analyses, the subjects were classified as normal weight(n=30) and overweight(n=54) groups based on a BMI cut-point of 23.0kg/m 2 . In the results, energy consump- tion were significantly different for commute time(p

The purpose of this study was to develop an exercise program for Bed-care the elderly. The Self bedside exercise program that include stretching of whole body, fine motor skill using bean-dumbbell, and motor coordination, with a total of 30 exercises in 3 stages. There is advanced research related to this result, it was noted that the implementation of the self-bedside exercise program for patients who participated in this study program reached 108.5±12.44% and the implementation showed a statistically positive ADL. Such, results can be seen as an indication that voluntary participation, the goal of this program, was well induced. It was surmised that the increase of volun- tary participation was affected by several factors: a familiar instrument called the bean-dumbbell was used, the goal setting of simple movement enhanced confidence of movement, and voluntary participation was possible.

Early diagnosis of breast cancer in very young women (30 years) is challenging and the characteristic imaging findings are not yet fully understood. We evaluated the imaging findings of breast cancer in very young women (30 years) and to correlate them with clinicopathological features.A total of 50 surgically confirmed breast cancers were included in our retrospective study. The medical records were reviewed and the radiological features were analyzed according to the new 5th edition of the ACR BI-RADS lexicon.The breast cancers in our study population most commonly presented as a self-detected mass (74%), T2-3 stage (58%), histological grade III (52.3%) and ER-positive (80%) subtype. The most common finding was an irregular (87.5%) hyperdense (66.7%) mass with indistinct margins (50%) on mammography and an irregular (75.6%) indistinct (57.8%) hypoechoic/heterogeneous (77.8%) mass without a posterior acoustic feature (60%) on ultrasonography. MRI revealed an irregular shape (63.3%), irregular margins (43.3%), and heterogeneous enhancement (60%) with washout kinetics (69.4%). Mammographically, microcalcifications were correlated with the HER2-enriched type, and mass-type lesions were correlated with triple-negative cancer (p=0.04). An oval/round mass on ultrasound (p=0.005), rim enhancement (p=0.004) and intralesional T2 high signal intensity (p=0.04) on MRI were associated with the triple-negative type.On all imaging modalities, breast cancer in very young women usually presented as an irregular mass, and certain radiological features could be used for predicting the specific tumor type.

The cause of continued suppression of serum thyroid-stimulating hormone (TSH) levels during antithyroid drug therapy in some Graves' patients is unclear. Recently, there has been a notable explanation involving the direct inhibition of TSH receptor antibody (TRAb) on TSH secretion in the pituitary gland. The purpose of this study is to verify the relation between TRAb or other clinical parameters and the continued suppression of serum TSH level during antithyroid drug therapy in patients with Graves' disease. We reviewed the medical records of patients with Graves' disease between 1995 and 2002 at Samsung Medical Center. We selected 167 Graves' patients who had been euthyroid for at least 12 months after recovery of serum T3 and T4 levels during the antithyroid drug therapy. We analyzed the correlation of the interval until recovery of serum TSH with the pretreatment clinical parameters. We compared the recovery rates of suppressed TSH levels between pretreatment thyrotrophin-binding inhibitory immunoglobulin (TBII)-positive (>15%) and TBII-negative patients. We also compared the clinical parameters between two groups at the time of diagnosis and after recovery of thyroid hormone. Pretreatment serum T3 level, (131)I uptake, TBII activity, and the time to recovery of T3 or T4/free T4 level showed significant positive correlations with the interval until recovery of serum TSH level ( p < 0.05). Recovery rates of serum TSH levels at 3 months after recovery of thyroid hormone were significantly lower in pretreatment TBII-positive patients than those in TBII-negative patients ( p < 0.01). Serum TSH levels were significantly lower in TBII-positive patients at 3 months after recovery of thyroid hormone ( p < 0.05). TBII activities inversely correlated only with serum TSH levels at 3months after recovery of thyroid hormone ( p < 0.001). In conclusion, continued suppression of serum TSH level may be attributed to TRAb activity as well as the pretreatment severity of thyrotoxicosis and the time to recovery of thyroid hormone in patients with Graves' disease during antithyroid drug therapy.

Objective: To investigate the heterogeneity of early-onset and ketosis-resistant diabetes and to define a not-arbitrary cut-off age for early-onset diabetes based on its clinical and metabolic characteristics, and diabetes complications. Methods: We classified 1015 early-onset diabetes subjects aged 21–40 into four groups (group I, age at diagnosis 21–25 years; group II, 26–30; group III, 31–35; group IV, 36–40). Familial and diabetic history, statue of insulin secretion, metabolic parameters, and diabetes complications were analyzed. Results: No significant difference in family history or the rate of diabetic complication was found in the four groups. Subjects with a 21 to a 25-year-old diabetes onset had the lowest serum C-peptide levels, with 50% of the cumulative 24-h urine C-peptide levels of the other three groups ( p < 0.0001). This group also had the lowest prevalence of hyperlipidemia and arterial hypertension ( p < 0.01 and

The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) is a fully automated, cartridge-based real-time PCR assay designed to detect Mycobacterium tuberculosis and rifampin resistance within 2 h. The performance of the Xpert assay has been evaluated in various clinical settings. However, there are few data comparing the Xpert assay to the Cobas TaqMan MTB test (Roche Diagnostics, Basel, Switzerland), one of the most widely utilized molecular assays for M. tuberculosis detection. In this prospective study, 320 consecutive respiratory specimens were processed simultaneously using acid-fast bacillus (AFB) staining, mycobacterial cultures with both solid and liquid media, and the Cobas and Xpert assays. The Xpert assay was performed with direct respiratory specimens, while the Cobas assay was done with decontaminated concentrated specimens. Based on the culture as a reference method, the overall sensitivities of the Cobas and Xpert assays were 71.4% and 67.9%, respectively. When AFB smear results were taken into consideration, the sensitivities of the Cobas assay for smear-positive and -negative specimens were 87% and 54%, while those of the Xpert assay were 67% and 69%, respectively. The Cobas assay showed 100% specificity and 100% positive predictive value (PPV) regardless of smear results, while the Xpert assay showed 100% specificity and 100% PPV for smear-positive specimens but 98% specificity and 60% PPV for smear-negative specimens. In conclusion, the Xpert assay showed performance that was slightly inferior to that of the Cobas assay but seems useful for the rapid detection of M. tuberculosis , considering that it was performed without laborious and time-consuming decontamination and concentration procedures.

To identify low-temperature-responsive genes in rice, we screened gus -trapped T-DNA tagging lines that had been subjected to cold stress at 5 °C. Out of 15,586 lines, 81 (0.52%) showed cold-responsive GUS activity. Among the 62 lines we selected for further study, 53 showed increased GUS activity while 9 showed less. In addition, 16 of those 62 lines were influenced by abscisic acid (ABA), suggesting an ABA-dependent cold response. We used inverse PCR or thermal asymmetric interlaced (TAIL) PCR to identify 37 tagged genes from those lines, and further characterized two of them at the molecular level. The OsRLK1 gene, which encodes a putative leucine rich repeat (LRR)-type receptor-like protein kinase, was inducible by cold and salt stresses. The OsDMKT1 gene, encoding a putative demethylmenaquinone methyltransferase (DMKT), was also inducible by low temperatures, but not by high salt or drought. The T-DNA-tagged OsDMKT1 gene also co-segregated with the cold-inducible gus gene. Our results indicate that the T-DNA tagging lines are useful in obtaining the stress-responsive genes in rice.

Among 59 Korean isolated, 20 were confirmed as members of the genusBifidobacterium species based on gram staining, microscopic examination of cell morphology and the TLC method. The oxygen tolerance and antioxidative activities of these 20Bifidobacterium strains and 5 standardBifidobacterium strains were tested. All the strains demonstrated antioxidative activities as regards inhibiting linoleic acid peroxidation. The antioxidative activities of isolated and standard strains were found to range from 10.7–46.4% and from 10.7–22.2%, respectively. In addition, all tested strains exhibited a scavenging ability on DPPH free radicals, range from 15–41% for the isolated strains and 8.3–22% for the standard strain. Accordingly, the isolatedBifidobacterium strains demonstrated higher antioxidative activities than the 5 standardBifidobacterium strains. On the base of grades for each test, HJL 7511 was identified as the best strain, followed by HJL 7501. 2 strains were identified with Polymerase Chain Reaction (PCR) assay using group-specific primers designed from the nucleotide sequences of the 16S rRNA and internal transcribed spacer (ITS) regions of the Bifidobacteria. Based on the sequencing results, HJL 7511 and HJL 7501 were identified asBifidobacterium infantis.

In order to obtain novel strains that hydrolyzed the rac-ketoprofen ethyl ester to an enantiomer of ketoprofen, we enriched strains from broad ecological niches in which the thermostable enzymes were ubiquitously found. The isolated strains were first analyzed to detect the ester-hydrolyzing activity by using a selective plate, and then further screened by activity on the (R,S)-ketoprofen ethyl ester. Twenty-six strains were screened primarily and further compared for the ethyl ester-hydrolyzing activity in terms of conversion yield and enantioselectivity. Consequently, a strain JY144 was isolated as a novel strain that produced a (R)-stereospecific esterase with a high stability and systematically identified as a Bacillus stearothermophilus JY144. The enzyme was indeed stable at a broad range of pH (6.0–9.5) and temperature, up to 65 °C. The optimal temperature and pH for enzymatic conversion were 50 °C and 9.0, respectively. Since the wild-type strain showed a poor cell growth and enzyme activity, we further attempted the cloning of esterase gene into Escherichia coli, with a simple and rapid strategy for selecting the positive clones, and determined its primary structure. The cloned gene had an open reading frame (250 amino acids) with a calculated molecular mass of 27.4 kDa. The primary structure showed a relatively high homology (38–52%) to probable esterases unidentified to date, and thus presumed as a novel family enzyme. In whole cell conversions, the recombinant enzyme had a superior potential than the parent strain, and it could completely convert the rac-ketoprofen ethyl ester to (R)-ketoprofen, with an optical purity of 99%.

Learning Classifier System (LCS) finds a new rule set using genetic algorithm (GA). In this paper, The Zeroth Level Classifier System (ZCS) is applied to evolving the strategy of a robot soccer simulation game (SimuroSot), which is a state varying dynamical system changed over time, as GBML (Genetic Based Machine Learning) and we show the effectiveness of the proposed scheme through the simulation of robot soccer.

Thirty plants of the Compositae family were screened for inhibitory activity of angiotensin converting enzyme (ACE). Among them, Chrysanthemum boreale Makino and Ixeris dentate Nakai were selected for further investigation since they had the highest inhibitory activity. Crude water extracts of the flowers of Chrysanthemum boreale Makino and the roots of Ixeris dentate Nakai were prepared by heating at 95℃ and 60℃ for 2 hr, respectively, followed by centrifugation at 8000×g for 30 min. Crude extracts were then filtered using YM-3 and YM-1 membranes. The ACE inhibitors were isolated using consecutive chromatographic methods including: Sephadex G-15, ion exchange, FPLC, and reverse phase HPLC. The inhibitors were identified to have molecular masses of 204 and 283 daltons, respectively, by mass spectrometry. These results demonstrate that crude extracts of Compositae plants may be useful as functional food ingredients with anti-hypertensive properties.

To isolate novel strains expressing an esterase that hydrolyzed the rac-ketoprofen ethyl ester to (S)-ketoprofen in the stereospecific manner, we screened broad ecological niches and soil samples in which the activity was expected to be found. Thousands of microbial strains were tested to determine their ester-hydrolyzing activity by using an agar plate containing insoluble tributyrin as an indicative substrate, and then further screened by activity on the (R, S)-ketoprofen ethyl ester. Twenty-eight strains were screened primarily and compared with respect to the potential to ketoprofen ethyl ester-hydrolyzing activity in terms of conversion yield and chiral specificity. Consequently, a strain S34 was isolated as a best producer and finally identified as a Pseudomonas sp. S34. We first formulated the optimal medium for the high level production of the enzyme, and as a preliminary experiment for enzymatic resolution, we characterized the fractionated enzyme. The enzyme with ketoprofen ethyl ester-hydrolyzing activity to (S)-ketoprofen showed a high degree of enantioselectivity (>94%) and was mainly found in cell extracts, whereas no distinct activity was detected in culture broth. The optimum pH and temperature of the enzyme were 9.5 and 35 °C, respectively. The activity of the enzyme was markedly increased (four-fold) by addition of a non-ionic detergent Triton X-100 and, resultantly, a high activity toward ketoprofen ethyl ester (52 U/mg) was found. The small-scale conversion of (R, S)-ketoprofen ethyl ester to (S)-ketoprofen using the partially purified enzymes was completed in 28 h, with optical purity of 99% and yield of 47%.

Aqualysin I, which is a subtilisin-type, extracellular protease secreted by Thermus aquaticus YT-1, is synthesized as a unique precursor bearing pro-domains at both N- and C-terminus of the mature protease domain as well as an N-terminal signal peptide. To investigate the function of the C-terminal pro-domain in maturation and export pathway of the precursor in E. coli cells, aqualysin I variants were constructed in which deletion mutants of the C-terminal pro-domain lacking its own signal peptide were inserted into pIN-III-ompA3. When E. coli harboring wild type and mutant plasmids were induced by 0.2 mM IPTG, active aqualysin I was produced by heat treatment at 65 °C. Aqualysin I precursors with deletions of more than 5 amino acid residues at the C-terminal end of pro-domain were much more rapidly processed than that of wild type, indicating that the C-terminal pro-domain functions as a inhibitor for processing of aqualysin I precursor. With the wild type, most of aqualysin I was present in membrane fraction (probably the outer membrane), whereas for the truncated mutants, it remained in the cytoplasm, indicating that for deletion mutants, their precursors expressed in cells were not translocated across the cytoplasmic membrane, despite the existence of an N-terminal signal peptide.

The international context has important implications for board interlock network dynamics. Drawing from an institutional logics perspective, we construct a theoretical framework linking the dynamic...

Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical (EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-dependent cancer has been reported rarely compared with the numerous cases of BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors (ERs). In a cell viability assay, BPA, BPS, and BPF significantly increased proliferation of MCF-7 CV cells compared to control (DMSO) as did 17β-estradiol (E2). In Western blotting assay, BPA, BPS, and BPF enhanced the protein expression of cell cycle progression genes such as cyclin D1 and E1. In addition, MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology by the treatment of BPA, BPS, or BPF for 24 hours. In cell migration assay, BPA, BPS, and BPF accelerated the migration capability of MCF-7 CV cells as did E2. In relation with the EMT process, BPA, BPS, and BPF increased the protein expression ofN-cadherin, while they decreased the protein expression of E-cadherin. When BPA, BPS, and BPF were co-treated with ICI 182,780, an ER antagonist, proliferation effects were reversed, the expression of cyclin D1 and cyclin E1 was downregulated, and the altered cell migration and expression ofN-cadherin and E-cadherin by BPA, BPS, and BPF were restored to the control level. Thus, these results imply that BPS and BPF also have the risk of breast cancer progression as much as BPA in the induction of proliferation and migration of MCF-7 CV cells by regulating the protein expression of cell cycle-related genes and EMT markersvia the ER-dependent pathway.

Purpose Although orthognathic surgeries focus on adjustment of facial asymmetry (FA), many clinicians know by experience that the natural head posture (NHP) also is corrected after the surgery. The authors examined whether this was indeed the case by the measuring the NHP during the course of orthognathic treatment. Factors associated with NHP correction also were evaluated. Patients and Methods In this retrospective study, clinical features, including the NHP, of patients with FA and those with facial symmetry (FS) were compared. They were outpatients of a private orthodontic dental clinic from December 2008 to March 2012. The degree of NHP tilt was evaluated using an interpupillary (IP) horizontal angle. The NHP of patients with FA were analyzed further before presurgical orthodontic treatment, after presurgical orthodontic treatment, after orthognathic surgery and postsurgical orthodontic treatment, and 1 year after completion of postsurgical orthodontic treatment. The NHP difference at each time point was analyzed using 1-way analysis of variance. An analysis of factors that influence NHP tilt correction was performed by linear regression. Results Thirty-one patients with FA and 27 with FS were evaluated. The NHP tilt was more profound in the FA group compared with the FS group. There were more patients with skeletal Class III in the FA group. The degree of NHP tilt in the FA group was decreased after orthognathic surgery and postsurgical orthodontic treatment and remained when measured 1 year later. Women were less prone than men to NHP tilt correction by orthognathic surgery. Conclusion Patients with FA have a tilted NHP compared with those with FS. Orthognathic surgery for FA might correct a tilted NHP to a lesser degree in women.

Breast plasmacytoma (BP) is an extremely rare extramedullary manifestation of multiple myeloma (MM). We report the imaging findings of an unusual case in which BP was the initial presentation of MM. A 53-year-old woman with no contributory medical history underwent chest computed tomography to evaluate intermittent nocturnal anterior chest pain, and bilateral multiple breast masses were found. Following an ultrasound-guided core needle biopsy, these lesions were confirmed to be BP.

3, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea Background: Recently, the iNtRON VRE vanA/vanB real-time PCR (iNtRON; iNtRON Biotechnology, Korea) assay, a multiplex real-time PCR method, was introduced. In this prospective study, we compared the iNtRON assay with the Seeplex VRE ACE detection kit (Seeplex; Seegene, Korea), a conventional multiplex PCR assay. Methods: A chromogenic agar-based culture, in which pre-selected vancomycin-resistant enterococci (VRE) was grown and subsequently plated on blood agar with vancomycin disks, was regarded as the reference method. A total of 304 consecutive rectal swab specimens were tested for VRE by culture and by iNtRON and Seeplex PCR assays. For the PCR assays, specimens were enriched for 16-24 hr before PCR. Results: VRE were isolated from 44 (14.5%) specimens by chromogenic agar-based culture. The clinical sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the iNtRON assay were 100% (95% confidence interval: 89.8%-100%), 99.2% (96.9%-99.9%), 95.6% (83.6%-99.2%), and 100% (98.2%-100%), respectively, while those of the Seeplex assay were 97.7% (86.2%-99.9%), 99.6% (97.5%-99.9%), 97.7% (86.2%-99.9%), and 99.6% (97.5%-99.9%), respectively. The iNtRON assay had a detection limit of 3,159 copies/μL and 13,702 copies/μL for the vanA and vanB genes, respectively. No cross-reactivity was observed in 11 non-VRE bacterial culture isolates. Conclusions: The overall performance of the iNtRON assay was comparable to that of a chromogenic agar-based culture method for prompt identification of VRE-colonized patients in hospitals. This assay could be an alternative or supportive method for the effective control of nosocomial VRE infection.

Painless legs and moving toes is an unusual syndrome, which has not previously been reported as an initial presentation of ischemic stroke. We encountered a 78-year-old woman who developed dysarthria and involuntary movement of her left toes that was clinically regarded as painless legs and moving toes. These symptoms appeared abruptly and simultaneously as the initial symptoms of stroke, and improved gradually with conservative management by intravenous hydration for a month. We suggest that, in our case, a cortical brain lesion caused by ischemic stroke might be associated with the development of painless legs and moving toes.

Commercial development at 63 rural and small-town Interstate exits is quantified and related to local market wealth, size, geography, access, traffic, site competition, and other development. Five development types (gas stations, convenience stores, fast food restaurants, sit-down restaurants, and motels) are studied. The geographic information system TransCAD 3.0 is used to determine network access and local trade area characteristics. Models are then estimated for each development type using classification and regression techniques separately and in combination. Model estimates are then compared with actual development. Results show that the relationships are complex, often nonlinear; and show high correlation between development types. The findings should be useful for planning exit land use, coordinating market assessments, determining the value of land, and assessing sites for business placement.

We attempted to improve antibody affinity by varying glycosylation on the light chain variable region. The human hybridoma line HB4C5 produces an antibody reactive to lung adenocarcinoma, which possess a N-glycosylated carbohydrate chain on the light chain hypervariable region. It has been shown that altering this carbohydrate structure can be accomplished by varying the level of N-acetylglucosamine in glucose free medium, a change in the carbohydrate chain could be induced which resulted in modifying antigen binding. By culturing the cells in media containing more than 20 mM N-acetylglucosamine, cells produced antibody with 10 fold improved affinity as compared with antibody produced in 20 mM glucose-containing medium. A newly induced light chain glycoform produced in the N-acetylglucosamine-containing medium was shown to be responsible for this antigen binding enhancement. Addition of glucose in the N-acetylglucosamine-containing media led to decreased antibody affinity and slightly inhibited production of a new light chain in a dose-dependent manner. Combination of 20 mM N-acetylglucosamine and 0.5 mM glucose gave a higher antibody production without the decrease of the antigen binding. These results indicate that optimization of N-glycosylation on the light chain, which leads to higher antigen binding, can be accomplished by adjusting a ratio of glucose and N-acetylglucosamine in the culture medium.

Tricho-rhino-phalangeal syndrome type I (TRPSI) is a rare autosomal dominant hereditary disorder characterized by sparse hair, bulbous nose, long philtrum, thin upper lip, and skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. TRPSI is caused by mutations in the TRPS1 gene. Herein, we report two Korean cases of TRPSI. Although both patients (a 17-year-old-female and a 14-year-old male) had typical clinical findings, Patient 1 had an additional growth hormone (GH) deficiency. Treatment with recombinant human growth hormone (rhGH) 0.7 IU/kg/week led to an increase in growth velocity. Over 10 years of GH therapy, the mean growth velocity was 5.7 ± 0.9 cm/year. However, the patient 2 did not show apparent GH deficiency by GH stimulation test, had a poor response with rhGH therapy and GH therapy was discontinued after 6 months. Upon genetic analysis of the TRPS1 gene, two mutations were found. Patient 1 had a heterozygous mutation c.2520dupT (p.Arg841LysfsX3) which had not been previously reported. Patient 2 had a known nonsense mutation c.1630C>T (p.Arg544X). In summary, we were the first to report Korean patients with mutation of TRPS1.

An experiment was conducted to investigate the supplementation of direct-fed microbials (DFM) as an alternative to antibiotics on growth performance, immune response, cecal microbial population, and ileal morphology of broiler chickens. A total of 800 one-day-old male broiler chicks (Ross × Ross) were randomly allotted to 4 dietary treatments with 4 replicate pens per treatment (50 birds/replicate pen). The 4 dietary treatments fed for 35 d were a corn-soybean meal basal diet (control); control plus 0.1% virginiamycin, as an antibiotic growth promoter (AGP); control plus 0.1% direct-fed microbials that contained Lactobacillus reuteri (DFM 1); and control plus 0.1% direct-fed microbials that contained a mixture of L. reuteri, Bacillus subtilis, and Saccharomyces cerevisiae (DFM 2). Results showed that dietary AGP and DFM supplementation significantly increased (P < 0.05) the BW gain of broilers during 0 to 21 d. The feed intake was reduced, whereas the feed conversion was improved significantly when birds were fed DFM 2 at 0 to 7 d of age. The white blood cell and monocyte levels were significantly higher in the DFM 2 group compared with the control. In addition, feeding DFM significantly (P < 0.05) increased the plasma immunoglobulin levels where a higher level was observed in DFM 2 compared with those of the other treatments. Neither DFM nor AGP treatments affected the cecal Lactobacillus and Salmonella content; however, cecal Escherichia coli content significantly decreased in broiler chickens fed DFM and AGP. The ileal villus height, and width and total thickness of muscularis externa were significantly increased when birds were fed DFM compared with AGP and control. These results indicate that the dietary supplementation of DFM increases the growth performance of birds at an early age, stimulates the immune response, decreases the number of E. coli, and improves the ileal morphology of broiler chickens. Thus, DFM that contained a mixture of several beneficial microorganisms could be a viable alternative to antibiotics in the broiler diets.

[Purpose] To examine changes in the knee joint's isokinetic muscle functions following systematic and gradual rehabilitation exercises lasting for 12 weeks for male and female patients who underwent anterior cruciate ligament (ACL) reconstruction. Differences in muscle functions between the uninvolved side (US) and the involved side (IS) before surgery, differences in muscle functions between US and IS after rehabilitation exercises lasting for 12 weeks, and changes in muscle functions on US and IS between before and after surgery were analyzed to examine the effects of accelerated rehabilitation exercises after ACL reconstruction. [Subjects] The study subjects were 10 patients, five females and five males, who underwent ACL reconstruction performed by the same surgeon. [Methods] As a measuring tool, a Biodex Multi-joint system 3pro (USA), which is an isokinetic measuring device, was used to examine the flexion and extension forces of the knee joint. During isokinetic muscle strength evaluation, the ROM of US was set to be the same as that of IS for consistency of measurement. [Results] At 60°/s, the isokinetic muscle functions of the females did not show any significant change between before and after surgery in any of the variables on both US and IS. At 60°/s, the isokinetic muscle functions of the males did not show any significant change between before and after surgery in the peak torque, average power, and entire work done on US. In extension, peak torque on IS did not show any significant change.

A gene, isp-B, encoding an intracellular serine protease from a newly isolated Bacillus sp. WRD-2 was cloned and characterized. Nucleotide sequence analysis showed an open reading frame of 960 bp encoding a polypeptide comprised of 319 amino acids. The primary structure of the enzyme predicted the structural features characteristic of other intracellular serine proteases, including active sites, Ser, His and Asp, as well as no signal sequence. The predicted amino acid sequence showed more than 60% homology with the intracellular serine proteases from Bacillus species. When expressed in E. coli, the recombinant enzyme (rISP-B) was overproduced in the cytoplasm as soluble and active form. The purified enzyme was completely inhibited by phenylmethylsulfonyl fluoride, EDTA and antipain. The enzyme showed maximum activity at pH 8.0 and 45 degrees C. It was stable atpH from 7.5 to 11.0 and below 50 degrees C.

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial myopathy commonly caused by deleterious changes in the mitochondrial DNA (mtDNA). We describe a 45-year-old man who was referred to us for investigation of progressive ptosis. We performed a multiplex ligation-dependent probe amplification (MLPA) assay of mtDNA from muscle tissue and peripheral blood leukocytes, and followed up with gap-polymerase chain reaction (PCR) and direct sequence analysis. Results showed a deletion of a 4,407 bp segment in the mtDNA region, ranging from nucleotide position 8,577 in the MT-ATP6 gene to nucleotide position 12,983 in the MT-ND5 gene. To the best of our knowledge, this is the first report of a CPEO patient with a large novel deletion of mtDNA genetically confirmed by MLPA assay. MLPA can be a feasible platform for clinical laboratories to detect large deletion mutations in the mtDNA for suspected cases.

To investigate thyroid-stimulating hormone receptor (TSHR) and thyroid peroxidase (TPO) mutations in Korean patients with primary congenital hypothyroidism (CH).Congenital hypothyroidism is a common genetic disorder in which the majority of mutations occur in the TSHR and TPO genes.We examined the frequencies of TSHR and TPO mutations among Korean patients with primary CH. Furthermore, we explored the relationships between imaging findings and mutation status.A total of 193 paediatric patients with nonsyndromic CH were enrolled in the present study.Patients with decreased (99m) Tc uptake were screened for TSHR mutations using Sanger sequencing, and those with increased uptake were screened for TPO mutations. The relationships between scintigraphic and ultrasonographic findings and mutation status were analysed.Thirteen (16·5%) of 79 patients with decreased (99m) Tc uptake were found to harbour TSHR mutations including G132R, G245S, R450H, R519C and F525S. The R450H mutation was present in 13 (72·2%) of 18 disease alleles. Seven (10·3%) of 68 patients with increased (99m) Tc uptake harboured TPO mutations including R189Q, K439E, G493S, C808LfsX72, A863T, R875Hfs and P883S. The TSHR and TPO mutations were observed only in patients with normal to slightly enlarged thyroid glands.This study identified underlying TSHR and TPO mutations in Korean patients with CH and revealed a possible relationship between imaging findings and mutation status. In addition, the low rate of mutation positivity suggests significant genetic heterogeneity of CH in the Korean population.

Breast ultrasonography (US) is recognized as a useful diagnostic tool for palpable or nonpalpable breast masses, but isoechoic lesions surrounded by fat can be a challenge for radiologists and can result in false-negative interpretations and a delayed diagnosis of breast cancer. Identifying isoechoic lesions surrounded with fat by using breast US requires meticulous evaluation with B-mode US in correlation with mammography. For correlation between mammography and US, the location, surrounding tissue, and lesion characteristics, including size, shape, and internal contents, must be considered. Complementary tools to B-mode US in the evaluation of isoechoic breast lesions include spatial compound imaging, tissue harmonic imaging, US elastography, color or power Doppler imaging, power Doppler vocal fremitus imaging, and contrast agent enhancement. Specimen radiography after breast biopsy can be helpful in evaluating the adequacy of tissue sampling and the appropriateness of lesion targeting and localization, evaluations that increase confidence in the findings from tissue acquisition.

Many clinical situations necessitate highly sensitive and reliable molecular assays; however, the achievement of such assays remains a challenge due to the inherent limitations of molecular testing methods. Here, we describe a simple and inexpensive enrichment technique that we call mutant enrichment with 3'-modified oligonucleotides (MEMO). The method is based on the use of a 3'-modified oligonucleotide primer that blocks extension of the normal allele but enables extension of the mutated allele. The performance of the technique was evaluated with respect to its ability to detect common cancer mutations in the EGFR, KRAS, BRAF, TP53, JAK2, and NPM1 genes. We achieved sensitivities of 10(-2) to 10(-6) using downstream Sanger sequencing, depending on the concentrations and thermodynamics of the primers. MEMO may be applicable to the quantitative real-time PCR platform and other downstream assays. This technique may be practically applicable to various medical situations.

Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. With the aim of establishing personalized medicine for treatment of solid tumors, we focused on MET amplification in gastric cancer patients, given the extreme sensitivity to c-Met inhibitor in MET amplified gastric cancer cell lines. We tested MET amplification and activation of c-Met in various gastric cancer cell lines and tissue samples from 482 gastric cancer patients who underwent curative surgery. Gastric cancer cell lines with MET amplification by quantitative real-time PCR (qPCR) and FISH predicted sensitivity to PHA-665,752, a selective c-Met kinase inhibitor. Of the 472 patients who had DNA sample available for qPCR analysis, 100 patients (21.2%) had a MET copy number greater than 4.0 copies and demonstrated poorer survival following curative surgery with statistical significance (5-year OS; 50.0 vs. 59.1%; MET amplification (+) vs. MET amplification (-); P = 0.0134). These results suggest that the increased MET copy number measured by qPCR plays an important role in determining prognosis in gastric cancer patients. However, the predictive role of MET amplification for treatment response should be further explored in upcoming clinical trials.

Nucleic acid-based amplification tests allow the rapid detection of Mycobacterium tuberculosis . Recently, a real-time PCR assay for M. tuberculosis complex, the Cobas TaqMan MTB test (Roche Diagnostics, Basel, Switzerland), was introduced. We performed a prospective study to evaluate the diagnostic performance of the Cobas TaqMan MTB test system. A total of 406 specimens collected from 247 patients were simultaneously tested by conventional culture, Cobas Amplicor MTB PCR, and TaqMan MTB PCR. The cross-reactivity with other Mycobacterium species and the detection limit were also evaluated. Among 406 specimens, a total of 24 specimens (5.9%) were culture positive: 14 specimens were positive by both TaqMan and Amplicor MTB PCRs, while 5 specimens were positive by only TaqMan PCR. The remaining five specimens were negative by both PCR methods. Seven specimens with negative culture results were positive by TaqMan PCR, but five of these were negative by Amplicor MTB PCR. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were 79.1%, 98.2%, 73.1%, and 98.7% for TaqMan and 58.3%, 99.5%, 87.5%, and 97.4% for the Amplicor MTB PCR test, respectively. There was no cross-reactivity with M. tuberculosis and nontuberculous mycobacterial species. The detection limit for the Cobas TaqMan MTB PCR test was 4.0 copies/μl. The Cobas TaqMan MTB PCR test showed higher sensitivity for detection of the M. tuberculosis complex without disturbing the specificity and NPV than the Amplicor MTB PCR test.

Investigations of naturally occurring mutations, such as the deletional thalassaemias and hereditary persistence of fetal haemoglobins (HPFHs), have brought many insights into human globin switching, but limited data have been reported so far. We selected 15 individuals with elevated fetal haemoglobin (HbF) levels (5%) from a previous screening of 27 006 Korean individuals and analysed dosage changes of the globin gene cluster using multiplex ligation-dependent probe amplification (MLPA). Dosage changes detected by the MLPA probes were followed up with gap-polymerase chain reaction and sequence analysis. Three subjects were found to have deletions in the globin gene cluster, including a beta-thalassaemia due to deletion of HBB (beta-globin gene), an HPFH due to deletions of HBD (delta-globin gene) and HBB, and an HPFH due to a novel HBG2-HBG1 fusion gene consisting of exons 1 and 2 of HBG2 ((G)gamma-globin gene) and exon 3 of HBG1 ((A)gamma-globin gene). The case with the HBG2-HBG1 fusion suggested the existence of another mechanism for the reactivation of HBG2 and HBG1. The IVS2 of HBG2 and HBG1might play a role in HbF regulation, and combinations of specific polymorphisms could influence the reactivation of these genes in adults.

With the development of dedicated receiver coils and increased gradient performance, 3.0-T magnetic resonance (MR) systems are gaining wider acceptance in clinical practice. The expected twofold increase in signal-to-noise ratio (SNR) compared with that of 1.5-T MR systems may help improve spatial resolution or increase temporal resolution when used with parallel acquisition techniques. Several issues must be considered when applying 3.0-T MR in the abdomen, including the alteration of the radiofrequency field and relaxation time, increase in energy deposition and susceptibility effects, and problems associated with motion artifacts. For the evaluation of liver lesions, higher SNR and greater resolution achieved with the 3.0-T system could translate into better detection of malignant lesions on T2-weighted images obtained with adjusted imaging parameters. For the evaluation of pancreatic and biliary diseases, high-resolution T2-weighted imaging using single-shot turbo spin-echo sequences is useful; improvement in SNR was noticeable on two-dimensional MR cholangiopancreatographic images. For the preoperative imaging of rectal cancer, a single-shot sequence is useful for dramatically decreasing imaging time while maintaining image quality. Substantial modification of examination protocols, with optimized imaging parameters and sequence designs along with ongoing development of hardware, could contribute to an increased role of the 3.0-T system for abdominal MR examinations.

0049-3848/$ see front matter © 2008 Elsevier Ltd. All rights reserv doi:10.1016/j.thromres.2008.04.014 encoded by the PROC gene on chromosome band 2q13, which is composed of 9 exons (1st exon is noncoding) [2]. Hereditary deficiency of PC (MIM# 176860) is a well-known genetic defect underlying hereditary thrombophilia [3]. Two types of PC deficiency exist. Type I deficiency is a quantitative defect and both PC activity and antigen levels are decreased. Type II deficiency is a qualitative defect and only PC activity is decreased, while the antigen level is normal. Approximately 90% of patients with PC deficiency have PC levels half of normal from a single mutation in PROC [4]. This condition is inherited in an autosomal dominant manner with incomplete penetrance, and clinically patients develop deep vein thrombosis (DVT) in lower extremities or fatal pulmonary embolism. Severe congenital PC deficiency is rare, comprising ~10% of PC deficiency, with undetectable or markedly decreased levels of PC activity or antigen from double mutations (homozygous or, less commonly, compound heterozygous) in PROC [4]. Most patients

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [(11)C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off-medication, two series of 15 trains of 5 Hz-frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (-4.9% and -6.5%, respectively) (P0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (-6.6%, P0.05 and -12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 +/- 14.1 to 32.0 +/- 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS.

Tongue tremor is a rare form of focal tremor. Even though the dysfunction of the dentato-rubro-olivary circular pathway has been proposed as its mechanism, the origin of the rhythmic activities remains unknown. We experienced a case of isolated tongue tremor after the removal of a cerebellar pilocytic astrocytoma. To localize the activated structures corresponding to the isolated tongue tremor, we analyzed subtracted ictal SPECT coregistered to MRI (SISCOM). SISCOM demonstrated multiregional hyperperfusion including the Guillain-Mollaret triangular and extratriangular structures. The activation of the inferior olive and red nucleus and accompanying extratriangular structures might be related to the isolated tongue tremor.

Thin films (20-150 nm thickness) of poly(o-anthranilic acid) with various doping levels were prepared on silicon substrates with deposited indium tin oxide, and their topography and current-voltage (I-V) characteristics were quantitatively investigated using current-sensing atomic force microscopy with a platinum-coated tip. The films were found to have a surface morphology like that of orange peel, with a periodic modulation and a surface roughness. The films exhibited nonuniform current flows and I-V characteristics that depended on the doping level as well as on the film thickness. Films with a high doping level were found to exhibit Zener diode switching behavior, whereas the films with a very low doping level (or that were dedoped) exhibited no current flow at all, and so are insulators. Interestingly, self-doped films (which are at an intermediate doping level) were found to have a novel electrical bistability, i.e., a switching characteristic like that of Schottky diodes, and increasingly insulating characteristics as the film thickness was increased. The films with thicknessor =62 nm, which exhibited this novel and stable electrical bistability, can potentially be used in the fabrication of high-density, stable, high-performance digital nonvolatile memory devices based only on transistors. The measured current images and I-V characteristics indicate that the electrical switching and bistability of the films are governed by local filament formation and charge traps.

Transcranial sonography (TCS) is potentially useful for the diagnosis of Parkinson's disease (PD). However, studies on TCS have so far been restricted to European populations. To investigate the efficacy of TCS in Korean PD patients and its correlation with the clinical features, we carried out midbrain TCS in 43 PD patients and 35 normal controls and evaluated the area of the substantia nigra (SN) hyperechogenicity and its ratio to the area of the whole midbrain. In 16 subjects (21%), TCS was unsuccessful due to insufficient acoustic temporal bone windows. The mean area of bilateral SN hyperechogenicity and its ratio to the midbrain area were greater in the PD patients than that in the controls (P < 0.01). In the PD patients, the area of SN hyperechogenicity and its ratio to the individual midbrain area were moderately correlated with the PD duration (r = 0.526 and 0.536, P = 0.01, respectively) but not with the age, UPDRS motor scores or H-Y stage. There was no difference in the SN hyperechogenicity between the tremor-dominant, akinetic-rigid, and mixed-type PD patients. In conclusion, midbrain TCS is an effective diagnostic tool for detecting PD in the Korean population. However, it does not reflect the severity or phenotypes of parkinsonism.

Olfactory deficit is known to occur frequently in Parkinson's disease (PD). This study aimed to explore olfactory deficit in PD and to investigate its possible correlation with the disease severity or the depth of the olfactory sulcus. Fifty-nine PD patients and 25 normal controls were examined by the odor identification test with the crosscultural smell identification test (CC-SIT). Among these subjects, the depth of the olfactory sulcus of 42 PD patients and 8 controls was measured in the plane of the posterior tangent through the eyeballs using the coronal view brain MRI. The CC-SIT scores of the PD patients were significantly lower than those of the normal control (P0.001). However, CC-SIT did not correlate with the disease duration, H-Y stage, score of UPDRS Part III, or the depth of either side of the olfactory sulcus (P0.05). Our study confirms that CC-SIT is a helpful test in detecting the olfactory deficit in Korean PD patients. The absence of correlation of olfactory deficit with the disease severity or the depth of olfactory sulcus may suggest that olfactory loss precede the development of motor signs and not be a primary consequence of damage to the olfactory sulcus.

A total of 437 human full-length cDNAs isolated by microarray analysis of liver and/or gastric cancer tissues were evaluated for their relevance to cancer using the fission yeast Schizosaccharomyces pombe. Overexpression of 161 human cDNAs in S. pombe caused growth inhibition and/or morphological changes, which can be considered as cancer-related phenotypes of S. pombe. Sixteen genes causing growth defects and morphological changes at the same time were chosen to validate their ostensible oncogenic properties. They were highly expressed in liver and/or gastric cancer cell lines. Also, when the mouse embryonic fibroblast cell type NIH3T3 was transfected with these genes, the proliferation rates of cells were increased by 32% to 120%. This study demonstrates that fission yeast can be used as an advantageous and powerful tool for the rapid screening of human genes relevant to cancer. Furthermore, the human genes screened can be tested further as diagnostic markers and potential therapeutic targets for liver and stomach cancers. They also can be studied further for the elucidation of mechanisms involved in carcinogenesis. (Journal of Biomolecular Screening 2007:568-577)