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Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7-membered and a 6-membered lactone ring based on spectroscopic analysis. During an unbiased screening of natural product libraries, this novel compound was found to dissociate amyloid-β (Aβ) plaques and tau tangles, which are key pathological hallmarks of Alzheimer's disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased Aβ-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets Aβ and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.

Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti-tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well-defined architecture. This review offers a comprehensive overview of dendrimer-based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune-suppressive responses (immune checkpoint inhibitors). On-going works and prospects of dendrimer-based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer-based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

OBJECTIVE There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p

The adductor muscle of the pen shell Atrina pectinata (AMPS) is a popular protein‐enriched food item in Asian Pacific countries, and has only been marketed in the frozen condition, as a result browning and decreased sensory attributes occur. To overcome these problems, superheated steam roasting (at 270°C for 4 min) combined with the hot smoke (10 min) using a selective Oak sawdust was employed to develop a new AMPS product yielding high physicochemical properties during storage periods (0–13 days) especially at 10°C. The processed AMPS showed high sensory preferences because of good odor, color, and textural properties. It also significantly inhibited bacterial growth, volatile basic nitrogen, thiobarbituric acid‐reactive species, and pH changes, and eventually possessed higher nutritional composition with low trimethylamine N‐oxide level. Results indicate that saturated steam allows AMPS at good physicochemical conditions, whereas hot smoke‐derived aroma compounds prolong its shelf life through antioxidant and antimicrobial activities.

Aims To conduct a systematic review and meta-analysis of epidemiological studies in order to assess quantitatively the effect of dairy consumption on risk of metabolic syndrome. Methods We searched for eligible studies published up to March 2015 through the PubMed and Embase databases and reviewed the references of relevant articles. Random-effects models were used to calculate the pooled relative risks with 95% CIs after adjusting for several confounders. Results We identified nine prospective cohort studies including a total of 35 379 subjects and 7322 incident cases of metabolic syndrome, and 12 cross-sectional studies including 37 706 subjects. In the meta-analysis of prospective cohort studies, the pooled relative risk of incidence of metabolic syndrome for the highest vs. the lowest category of dairy consumption was 0.85 (95% CI 0.73–0.98), and for a 1-serving/day increment of dairy consumption, the pooled relative risk was 0.88 (95% CI 0.82–0.95). In the meta-analysis of cross-sectional studies, the pooled relative risk of prevalence of metabolic syndrome for the highest vs. the lowest category of dairy consumption was 0.73 (95% CI 0.63–0.86). The association was not significantly different by geographical region, follow-up time and adjustment factors. Conclusion Our findings indicate that dairy consumption is inversely associated with the incidence and prevalence of metabolic syndrome. Further well-designed cohort studies and randomized controlled trials are warranted to provide definitive evidence.

Aim Mixed grain, which contributes to lowered glycaemic responses, has been shown to be effective in dietary management of patients with impaired glucose tolerance or diabetes. Methods The present study determined the postprandial blood glucose response of 20 healthy volunteers to mixed grains containing giant embryonic rice (MG-GER) or giant embryonic brown rice (MG-GEBR) compared with white rice (WR) in a randomised crossover design. Plasma glucose and serum insulin at 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes were measured, and glycaemic index (GI) and incremental area under the curve (iAUC) were calculated. Results The GIs for WR, MG-GER and MG-GEBR were 86.75 ± 5.78, 76.09 ± 7.01 and 69.33 ± 6.54, respectively. The 120-minute iAUCs after administration of MG-GER or MG-GEBR were significantly lower than that of WR. In addition, the MG-GEBR diet group had a significantly lower C-peptide concentration at the 120-minute time point when compared to the WR group. Conclusions These results suggest that consumption of MG-GER or MG-GEBR instead of WR is more effective to reduce postprandial glucose levels without increasing insulin secretion.

Centers for Neuro-Medicine, Neuroscience and Theragnosis, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea. *E-mail: yskim@bio.kist.re.kr Biological Chemistry Program, Korea University of Science and Technology (UST), Daejeon 305-350, Republic of Korea Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea kYonsei University Wonju College of Medicine, Gangwon-do 220-701, Republic of Korea Molecular Imaging Research Center, Korea Institute of Radiological &Medical Sciences (KIRAMS), Seoul 139-706, Republic of Korea Received October 30, 2014, Accepted January 14, 2015, Published online April 27, 2015

Black rice bran contains phenolic compounds of a high antioxidant activity. In this study, the 40% acetone extract of black rice bran was sequentially fractionated to obtain 5 fractions. Out of the 5 fractions, ethyl acetate fraction was subfractionated using the Sephadex LH-20 chromatography. The antioxidant activity of phenolic compounds in the extracts was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, 2,2-azino-bis-(3-ethylenebenzothiozoline-6-sulfonic acid) (ABTS) radical cation assay, reducing power. The subfraction 2 from ethyl acetate fraction had the highest total phenolic contents (TPC) (816.0 μg/mg) and the lowest EC50 values (47.8 μg/mL for DPPH radical assay, 112.8 μg/mL for ABTS radical cation assay, and 49.2 μg/mL for reducing power). These results were 3.1, 1.3, and 2.6 times lower than those of butylated hydroxytoluene (BHT), respectively. At a concentration of 100 μg/mL, the antioxidant activity and TPC of various extracts was closely correlated, with correlation coefficients (R(2) ) higher than 0.86. The major phenolic acid in subfraction 2 was identified as ferulic acid (178.3 μg/mg) by HPLC and LC-ESI/MS/MS analyses. Our finding identified ferulic acid as a major phenolic compound in black rice bran, and supports the potential use of black rice bran as a natural source of antioxidant.

GABA is the major inhibitory transmitter in the brain and is released not only from a subset of neurons but also from glia. Although neuronal GABA is well known to be synthesized by glutamic acid decarboxylase (GAD), the source of glial GABA is unknown. After estimating the concentration of GABA in Bergmann glia to be around 5-10 mM by immunogold electron microscopy, we demonstrate that GABA production in glia requires MAOB, a key enzyme in the putrescine degradation pathway. In cultured cerebellar glia, both Ca(2+)-induced and tonic GABA release are significantly reduced by both gene silencing of MAOB and the MAOB inhibitor selegiline. In the cerebellum and striatum of adult mice, general gene silencing, knock out of MAOB or selegiline treatment resulted in elimination of tonic GABA currents recorded from granule neurons and medium spiny neurons. Glial-specific rescue of MAOB resulted in complete rescue of tonic GABA currents. Our results identify MAOB as a key synthesizing enzyme of glial GABA, which is released via bestrophin 1 (Best1) channel to mediate tonic inhibition in the brain.

Background and Aim Hepatitis B virus (HBV) replication detected before the resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral agents. However, management strategy for patients with preoperatively undetectable HBV DNA without antiviral therapy is not clearly delineated. This study investigated viral reactivation after the liver resection in non-replicating HBV DNA-related HCC patients and its impact on the surgical outcome. Methods From 198 patients that underwent liver resection due to HBV-related HCC, 101 patients who had serially checked serum HBV DNA were analyzed. Results From 101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients (11/33, 33.3%) had viral replication after the liver resection. The postoperative viral reactivation (HR: 2.144; 95% CI: 1.122–4.097; P = 0.021), along with the existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376–6.689; P = 0.006), existence of microvascular invasion (HR: 2.479; 95% CI: 1.303–4.718; P = 0.006), and HBeAg positivity (HR: 2.059; 95% CI: 1.155–3.670; P = 0.014) predicted recurrence after the surgery. Quantification of intrahepatic total and covalently closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA was undetectable without the use of antiviral agent. Amount of intrahepatic cccDNA expressed as copies/hepatocyte in patients with postoperative viral reactivation showed significantly higher than those in patients with sustained negative serum HBV DNA (P = 0.010). Conclusions This study shows that naturally suppressed preoperative HBV without application of antiviral agent does not ensure undetectable serum HBV after the surgery, and postoperative viral reactivation might be associated with HCC recurrence.

Background/Aims Microvascular invasion (MVI) is a well-known prognostic factor of postoperative recurrence and of overall survival (OS) in patients with hepatocellular carcinoma (HCC). We compared the treatment outcomes of transarterial chemoembolization (TACE) and surgery/radiofrequency ablation (RFA) according to the presence of MVI in patients with early or late recurrent HCC that presented as Barcelona Clinical Liver Cancer (BCLC) stage 0 or A after curative resection for HCC. Methods A consecutive 68 patients with recurrent HCC of BCLC stage 0 or A at our institution between 1998 and 2012 were retrospectively enrolled. We compared the outcomes of patients treated by TACE or surgery/RFA. Tumor recurrence after curative resection was classified as early (≤ 12 months) or late (> 12 months) recurrence. Results Median tumor size was 1.5 cm (range, 1–10 cm), and 67 (98.5%) had HCCs within the Milan criteria. Median post-retreatment follow-up duration was 27 months (range, 1–109 months). Of the 68 patients, 19 (27.9%) underwent surgery/RFA, 47 (69.1%) TACE, and 2 (2.9%) were lost to follow-up. After retreatment, TACE showed significantly higher OS and recurrence-free survival rates than surgery/RFA in MVI-positive patients (P = 0.03 and P = 0.05, respectively), but not in MVI-negative patients (P = 0.95 and P = 0.98, respectively). In particular, in early recurred MVI-positive patients, TACE had a significantly higher OS rate than surgery/RFA (P = 0.01). Conclusions TACE may be the more effective treatment option for recurrent HCC of BCLC stage 0 or A than surgery/RFA in MVI-positive patients, especially in those that recur early after curative resection.

To evaluate the long-term efficacy and safety of levetiracetam based on a large population of patients in a tertiary epilepsy centre.All patients who received levetiracetam at the Seoul National University Hospital between January 2007 and March 2009 were evaluated. Patients who underwent brain surgery for seizure control or who had associated progressive disease were excluded from this study. The electronic medical records of these patients were reviewed retrospectively.A total of 568 patients were recruited, including 124 patients with generalised epilepsy. The mean duration of the follow-up period was 29.3 months. The seizure-free rate was 33.6% and was higher in patients with generalised epilepsy (51.6%) than patients with localisation-related epilepsy (28.6%). There was a strong correlation between initial response and dose-up response in 351 patients with increased dosage during the follow-up period. A total of 486 adverse events developed in 316 patients. The most common adverse event (24.3%) was irritability, which was associated with a high rate of drug discontinuation. Previous history of mood disorder was the only factor related to the development of irritability in patients using this medication.Levetiracetam was effective and safe as monotherapy and add-on therapy for partial and generalised epilepsy. The initial response to levetiracetam may provide useful information for predicting the response to increased dose of levetiracetam. However, the use of this medication was associated with a rate of irritability that was higher than expected in patients with a history of mood disorders.

Gross vascular calcification seen on imaging studies is common in hemodialysis (HD) patients, and is a significant predictor for cardiovascular mortality in HD patients. We have reported that arterial microcalcification (AMiC) of the vascular access is associated with increased aortic stiffness. This study investigated the impact of vascular access AMiC on cardiovascular mortality in HD patients. The study included 149 HD patients (mean age: 59.1 ± 13.9 years, 86 men and 63 women, 65.8% diabetic) who underwent vascular access surgery. Radial or brachial artery specimens were obtained intraoperatively, and pathologic examination was performed using von Kossa stain to identify AMiC. We compared all-cause and cardiovascular mortality between patients with and without AMiC. The mean follow-up was 37.8 ± 34.5 months, and AMiC was present in 38.8% (n = 57) of patients. The presence of diabetes (odds ratio: 16.49, 95% confidence interval: 1.81-150.36, P = 0.013) was the only independent risk factor for vascular access AMiC. During the observational period, there were 27 cardiovascular deaths. Kaplan-Meier analysis showed an increased cardiovascular mortality risk (log rank = 4.83, P = 0.028) in AMiC patients, and Cox regression analysis confirmed that AMiC was an independent predictor for cardiovascular mortality (hazard ratio: 2.35, 95% confidence interval: 1.09-5.09, P = 0.030). In conclusion, vascular access AMiC is a strong risk factor for cardiovascular mortality in HD patients.

Background An optimized pre-operative planning framework for lumbar spinal fusion was proposed, which augmented a novel functionality of suggesting optimal insertion trajectories and the screw size, considering operational safety and vertebra–screw interface strength, autonomously. Methods Based on an accurate 3D pedicle model with pre-operative computed tomography (CT) data, the framework begins with safety margin estimation for each potential insertion trajectory, followed by procedures to collect a set of insertion trajectories satisfying the operation safety objective. Among the trajectory candidates, the insertion trajectory, which maximized the insertable depth of a pedicle screw into the vertebral body, was then chosen as optimal, because the insertable depth enhanced the strength of the screw–vertebra interface. The radius of a pedicle screw was chosen as 70% of the pedicle radius. Results This framework has been tested on 176 spinal pedicles of 20 patients requiring spinal fusion. It was successfully applied, resulting in an average success rate of 100% and a final safety margin of 2.1 ± 0.2 mm. Planning accuracy and usefulness of the proposed surgical planner show significant differences compared with a conventional manual planner. Conclusion We can expect that the derived conservative safety margin mitigates screw misplacement or pedicle breach, despite potential errors induced during registrations or intraoperative screw insertion. Copyright © 2012 John Wiley & Sons, Ltd.

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

Symptomatic cytomegalovirus (CMV) infection in immunocompetent patients has traditionally been considered to have a benign and self-limited course. Moreover, current concept is that CMV infection in immunocompetent patients does not require treatment. However, recent studies reveal that CMV infection in immunocompetent patient with clinical manifestation is not a rare condition as thought previously. Here, we report a case of CMV colitis, which occurred in an immunocompetent hemodialysis patient who neither had HIV infection nor had medication that could cause immunosuppression. Our case revealed that the conservative treatment was not enough, and the administration of ganciclovir was essential for improving the disease course.

The antimicrobial action of amphipathic anti- microbial peptides (AMPs) generally depends on perturbation of the bacterial membrane via electrostatic interactions pro- moting initial binding to the surface and hydrophobic inter- actions for pore formation into the membrane. Several studies have focused on the structure-activity relationship (SAR) of AMPs by modulation of structural parameters. However, modulation of one parameter commonly induces simulta- neous changes in other parameters, making it difficult to investigate the specific influence of a single variable. In the present work, we investigated the distribution effect of cationic amino acids on the hydrophilic surface of the helical wheel using model AMPs composed of only lysine (K) and leucine (L) as representative cationic and hydrophobic residues, respectively, under conditions in which other parameters are fixed. Based on SAR analyses of a-helical KL model AMPs displaying different cationic distributions, we propose that the dispersity of cationic amino acids on the hydrophilic surface is a factor that contributes to the antimicrobial activity of AMP. Moreover, antimicrobial activity is enhanced by rearrangement of cationic amino acids to promote dispersed distribution. We confirmed the cationic distribution effect using natural AMP- derived a-helical CRAMP18 and its analogs. Our data show that accumulation of lysine shifts in the CRAMP18 analog leads to higher dispersion, and subsequently to improved anti- microbial activity. Therefore, we propose that the cationic distribution effect can be applied for the rational redesign of amino acid sequences to improve the antimicrobial activities of natural a-helical AMPs, in combination with regulation of other known structural parameters. Biotechnol. Bioeng. 2010;107: 216-223. 2010 Wiley Periodicals, Inc.

Human embryonic stem (hES) cells can be guided to differentiate into ventral midbrain-type neural precursor (NP) cells that proliferate in vitro by specific mitogens. We investigated the potential of these NP cells derived from hES cells (hES-NP) for the large-scale generation of human dopamine (DA) neurons for functional analyses and therapeutic applications. To address this, hES-NP cells were expanded in vitro for 1.5 months with six passages, and their proliferation and differentiation properties determined over the NP passages. Interestingly, the total hES-NP cell number was increased by > 2 × 104-folds over the in vitro period without alteration of phenotypic gene expression. They also sustained their differentiation capacity toward neuronal cells, exhibiting in vitro pre-synaptic DA neuronal functionality. Furthermore, the hES-NP cells can be cryopreserved without losing their proliferative and developmental potential. Upon transplantation into a Parkinson’s disease rat model, the multi-passaged hES-NP cells survived, integrated into the host striatum, and differentiated toward the neuronal cells expressing DA phenotypes. A significant reduction in the amphetamine-induced rotation score of Parkinson’s disease rats was observed by the cell transplantation. Taken together, these findings indicate that hES-NP cell expansion is exploitable for a large-scale generation of experimental and transplantable DA neurons of human-origin.

Previously, we found that baculoviral polyhe- drin (Polh) can successfully be used in Escherichia coli as a fusion partner for the expression of special foreign proteins as inclusion bodies, and the resulting, easily isolatable Polh-induced fusion inclusion bodies had almost the same characteristics as the native Polh. Here, we inves- tigated the effects of co-expression of baculoviral FP25 protein on Polh-induced inclusion-body production in an E. coli expression system, as FP25 is known to be involved specifically in polyhedra formation. Using several analytical tools, including SDS-PAGE, pronase proteolysis, solubiliza- tion under alkaline conditions, and electron microscopy, we found that co-expressed FP25 was associated with Polh- induced inclusion bodies and that its co-expression led to formation of compact inclusion bodies as well as high production levels. We confirmed that FP25 co-expression induced higher production levels of other heterologous protein, antimicrobial peptide Hal18, fused with aggrega- tion-prone Polh. Therefore, co-expression of baculoviral FP25 can be promisingly used to increase the levels of baculoviral Polh-fused foreign proteins, especially harmful proteins, expressed as inclusion bodies in an E. coli expression system. Biotechnol. Bioeng. 2007;96: 1183-1190.

Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.

Gas chromatography–mass spectrometry analysis revealed that primary roots of maize contain 28-norcastasterone (28-norCS) and its biosynthetic precursors, cholesterol, and cholestanol, which suggests that the C27-brassinosteroid (C27-BR) biosynthetic pathway to generate 28-norCS is operative in the roots. A cell-free enzyme solution prepared from maize roots successfully mediated C24-methylation of 28-norCS to produce castasterone (CS) with the aid of S-adenosyl-l-methionine, which indicates that CS can be generated through C27-BR biosynthesis, as well as C28-BR biosynthesis, in maize roots. Enzymatic conversion study using the cell-free enzyme solution demonstrated that CS is converted into 26-norCS in the enzyme solution. Exogenously applied 28-norCS and 26-norCS showed less activity than CS in the activation of gravitropic curvature and inhibition of root elongation. Taken together, a steady-state level of CS, the active BR in maize roots, seems to be strictly controlled by complicated processes such as C28- and C27-BR biosynthesis and biodegradation by C26-demethylation to exert its biological activity.

Src family non-receptor tyrosine kinases are involved in signaling pathways which mediate cell growth, differentiation, transformation and tissue remodeling in various organs. In an effort to elucidate functional involvement of p60c-Src (c-Src) in spermatogenesis, the postnatal changes in c-src mRNA and c-Src protein together with kinase activity and subcellular localization were examined in mouse testes. c-src mRNA levels in testes increased during the first 2 weeks of postnatal development (PND). Following a decrease at puberty (PND 28), the c-src mRNA levels re-increased at adulthood (PND 50). Src kinase activity of testes was low at PND 7 but sharply increased prepubertally (PND 15) and highest at adulthood. Upon Western blotting, the level of c-Src protein was the highest in prepubertal testes but rather decreased in adult testes at PND 50. In adult testes, ubiquitination of c-Src proteins was apparent compared with immature one at PND 7, suggesting active turnover of c-Src by ubiquitination. In immature testes, c-Src immunoreactivity was largely found in the cytoplasm of the Sertoli cells. By contrast, in pubertal and adult testes intense immunoreactivity was localized at the adluminal and basal cytoplasm of Sertoli cells bearing elongated spermatids and early germ cells, respectively. The immunoreactivity of c-Src in the Leydig cells was increased during pubertal development, suggesting the functional involvement of c-Src in differentiated adult Leydig cells. Throughout postnatal development, some spermatogonia and spermatocytes showed intensive c-Src immunoreactivity compared with other germ cells, suggesting a possible role of c-Src in germ cell death. Taken together, it is suggested that c-Src may participate in the remodeling of the seminiferous epithelia and functional differentiation of Leydig cells during the postnatal development of mouse testes.

This study examines how brassinolide (BL) and ethylene interact in the gravitropic response mechanism of maize (Zea mays) primary roots. When applied exogenously, ethylene increases the rate of gravitropic curvature in a dose-dependent manner. This effect of ethylene was confirmed by the fact that AVG, a specific action inhibitor of ACC synthase, reduces the gravitropic curvature in the presence and absence of BL. Since AVG did not inhibit BL-increased gravitropic curvature completely, we investigated the possibility that BL may act on the gravitropic response by ways other than simply through enhanced ethylene production. We show that BL exhibits some of its stimulatory effect in the absence of ethylene. In addition, BL reduces the presentation time and lag period for the gravitropic response, whereas ethylene increases them. One possible mechanism of such action is that BL affects protein kinase activity, since the protein kinase inhibitors, staurosporine and H89, reduce BL-increased gravitropic curvature. In summary, BL is involved in the gravitropic response in maize primary roots via ethylene production, but it acts in a way that differs somewhat from that of ethylene.

The functional recovery state of renal transplants can be divided into three types: immediate graft function (IGF), slow graft function (SGF) and delayed graft function (DGF). In contrast to the well-known clinical outcomes for IGF and DGF, the pathological findings and clinical outcomes of SGF are undetermined. This study evaluated possible clinicopathological correlations in 237 patients with SGF compared with patients with IGF. IGF and SGF were defined by serum creatinine levels (IGF < 1.2 mg/day 1; SGF: ≥1.2 mg/dL) at day 14 after renal transplantation. Graft biopsy was performed on this day, and pathological classification was performed using the Banff schema. The SGF group of patients (n = 121) showed higher rates of cadaver donors and male recipients than the IGF group (n = 116), but there were no significant differences in recipient or donor age, numbers of HLA mismatches, types of immuno-suppressant or follow-up periods between two groups. The SGF group showed higher serum creatinine levels at discharge, and a higher incidence of acute rejection than the IGF group (24.8% vs. 8.6%, P < 0.05) and lower graft survival rates (1 year, 93.3% vs. 100%; 5 years, 85.4% vs. 98.6%, respectively; P < 0.05). The presence of acute rejection in the SGF patients indicated a significantly decreased 5-year survival rate compared with the IGF group. The SGF group of patients with borderline pathology had a higher incidence of acute rejection than the IGF group, and significant increases in the expression of mRNA for pro-apoptotic genes (Fas-ligand, granzyme B and perform) compared with the IGF group. In conclusion, SGF represents the activated immune state and is associated with poor graft outcome. Anti-rejection treatment or modified immunosuppressive regimen may thus be indicated for patients with SGF.

A mixed coupling structure is proposed for the cross coupling of a comb-line filter. The proposed structure consists of an electric coupling probe and a magnetic coupling window, and the coupling required for the cross coupling of a cross-coupled filter can be achieved with much easier tuning capability than the structure with only an electric probe. A four-pole comb-line filter is designed and fabricated with the use of the proposed structure, and showed good filter response. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 20–23, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10505

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant type of brain cancer and has poor prognosis with a median survival of less than one year. While the structural changes of tumor cell surface carbohydrates are known to be associated with invasive behavior of tumor cells, the cell surface glycoproteins to differentiate the low- and high-grade glioma cells can be potential diagnostic markers and therapeutic targets for GBMs. In the present study, lectin arrays consisting of eight lectins were employed to explore cell surface carbohydrate expression patterns on low-grade oligodendroglioma cells (Hs683) and GBM cells (T98G). Griffonia simplicifolia I (GS I) was found to selectively bind to T98G cells and not to Hs683 cells. For identification of the glioblastoma-specific cell surface markers, the glycoproteins from each cell type were captured by a GS I lectin column and analyzed by LC-MS/MS. The identified proteins from the two cell types were quantified using label-free quantitative analysis based on spectral counting. Of cell surface glycoproteins showing significant increases in T98G cells, five proteins were selected for verification of both protein and glycosylation level changes using western blot and GSI lectin-based immunosorbent assay. This article is protected by copyright. All rights reserved

When an FM–CW radar is used to measure the target distance, the nonlinear relationship between the VCO control voltage and the output frequency has an adverse effect on the measurement accuracy. This paper presents a new technique to compensate for the VCO nonlinearity using a phase correction function derived from a calibration signal. To demonstrate the validity of the presented technique, an indoor experiment was conducted, and the results show a marked improvement in the shape of the range profile and the range resolution. © 2000 John Wiley & Sons, Inc. Microwave Opt Technol Lett 25: 266–269, 2000.

BACKGROUND A retrospective study of patients undergoing stereotactic radiosurgery for one to four brain metastases from nonsmall lung cell carcinoma (NSCLC) was performed to document outcomes and risks. METHODS Seventy-seven patients underwent radiosurgery during a 7-year interval; 71 also underwent whole brain radiation therapy. Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival. RESULTS The overall median survival was 10 months after radiosurgery, and 15 months from the diagnosis of brain metastases. Five factors significantly affected survival: extent of systemic disease, presence of a neurologic deficit, size of the intracranial tumor, initial imaging appearance of intratumoral necrosis, and initial resection of the primary tumor of the chest. Median survival time was 26 months in a subgroup of patients with no extracranial metastases, no neurologic deficits, and a small tumor without necrosis. The authors evaluated 91 tumors with imaging. Local tumor control was achieved in 77 lesions (85%) and tumoral radiation necrosis developed in 4 lesions (4.4%). Nineteen new metastatic tumors developed during the observation interval. CONCLUSIONS Stereotactic radiosurgery for NSCLC brain metastases is effective and is associated with few complications. The early detection of brain metastases and treatment with radiosurgery combined with radiation therapy provide the opportunity for extended high quality survival. Cancer 1997; 80:2075-83. © 1997 American Cancer Society.

We built a test-bed of a hybrid fiber radio (HFR) system for 60 GHz millimeter-wave wireless communication. Transmission at 155 Mbps over 24 km of an optical link with a tolerable BER less than 10−6 was achieved over the pico-radio cell with a radius of 2.6 m, which confirms the feasibility of 60 GHz HFR systems. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 328–330, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10311

Department of Industrial Technology, Dankook University, Cheonan 330-714, KoreaReceived September 12, 1998Notes Bull. Korean Chem. Soc. 1999, Vol. 20, No. 2 229Among corticoids, hydrocortisone 1 which is the majorhormone secreted by the human adrenal cortex is widelyused for the therapeutic purpose.

Agency for Defense Development, P.O. Box 35-5, Yuseong, Taejon 305-600, KoreaReceived February 23, 2001Keywords : Halocyclization, Stereoselectivity, 2,5-Substituted tetrahydrofurans, γ-Hydroxyalkenes.Methodologies based on the electrophilic halocyclizationof γ-unsaturated alcohols to tetrahydrohyfurans (THFs),which are widely occurring sub-units in several classes ofnatural products, have been well established over the fewdecades.

These events strongly suggested the presence of BRsin the lower plant, and led us to investigate the occurrence ofBRs in naturally-grown M. polymorpha .Whole bodies of naturally-grown M. polymorpha (4.3 Kg)were homogenized and extracted with 80% methanol (4 L ×3). The extracts were concentrated to aqueous phase in vacuoand re-extracted with chloroform (1 L×4). After reducingto dryness in vacuo, the chloroform fraction was solvent-partitioned between n-hexane and 80% methanol (1 L × 3).The concentrated residue of the 80% methanol soluble frac-tion was partitioned again between phosphate buffer (pH7.8) and ethyl acetate (1 L × 3). The concentrated ethylacetate soluble fraction (23.1 g) was purified by silica gelcolumn chromatography (150 g, Merck) eluted stepwisewith chloroform containing 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20,50 and 100% methanol (100 mL each). The fractions elutedwith 4-8% methanol in chloroform showed activity based onthe rice lamina inclination assay. The fractions were combin-ed (3.9 g), dissolved in 50% methanol (100 mL), andsubjected to ODS column (100 mL, Merck LiChroprep RP-18) chromatography. The elution was carried out with aque-ous methanol increasing the methanol content every 10%from 50% to 100% (100 mL each). The biologically activefractions eluted with 70-90% methanol were concentratedand loaded on Sephadex LH-20 column (bed volume 340mL, 22 × 900 mm) eluted with a mixture of methanol-chloroform (4 : 1) at a flow rate of 0.5 mL min