ADFCNN: Attention-Based Dual-Scale Fusion Convolutional Neural Network for Motor Imagery Brain-Computer Interface.

Convolutional neural networks (CNNs) have been successfully applied to motor imagery (MI)-based brain-computer interface (BCI). Nevertheless, single-scale CNN fail to extract abundant information over a wide spectrum from EEG signals, while typical multi-scale CNNs cannot effectively fuse information from different scales with concatenation-based methods. To overcome these challenges, we propose a new scheme equipped with attention-based dual-scale fusion convolutional neural network (ADFCNN), which jointly extracts and fuses EEG spectral and spatial information at different scales. This scheme also provides novel insight through self-attention for effective information fusion from different scales. Specifically, temporal convolutions with two different kernel sizes identify EEG µ and ß rhythms, while spatial convolutions at two different scales generate global and detailed spatial information, respectively, and the self-attention mechanism performs feature fusion based on the internal similarity of the concatenated features extracted by the dual-scale CNN. The proposed scheme achieves the superior performance compared with state-of-the-art methods in subject-specific motor imagery recognition on BCI Competition IV dataset 2a, 2b and OpenBMI dataset, with the cross-session average classification accuracies of 79.39% and significant improvements of 9.14% on BCI-IV2a, 87.81% and 7.66% on BCI-IV2b, 65.26% and 7.2% on OpenBMI dataset, and the within-session average classification accuracies of 86.87% and significant improvements of 10.89% on BCI-IV2a, 87.26% and 8.07% on BCI-IV2b, 84.29% and 5.17% on OpenBMI dataset, respectively. What is more, ablation experiments are conducted to investigate the mechanism and demonstrate the effectiveness of the dual-scale joint temporal-spatial CNN and self-attention modules. Visualization is also used to reveal the learning process and feature distribution of the model.

Retrospective Cohort Study to Compare Anesthesia in Living Donor Liver Transplantation Recipients Who Received Single and Dual Liver Grafts.

OBJECTIVE: Dual graft living donor liver transplantation (LDLT) is an alternative way to overcome small-for-size syndrome in LDLT. Surgical technique and outcome of using dual grafts have been reported, but there are no reports regarding anesthetic management. The aim of the current study is to compare the anesthetic management of single graft and dual graft liver transplantation. METHODS AND PATIENTS: Anesthesia records of 24 single graft liver transplantation recipients (GI) and 6 dual graft recipients (GII) were reviewed, analyzed, and compared retrospectively. Patient characteristics and intraoperative data between groups were compared with Mann-Whitney t test and Fisher's exact test where appropriate. P value less than .05 was regarded as significant. RESULTS: Patient characteristics and most of the intraoperative data were similar between groups. Significant difference was noted in the total anesthesia time and the anhepatic time. Both times were significantly longer in GII compared to GI. CONCLUSION: Dual graft living donor liver transplantation is surely a technically more challenging and demanding procedure. Therefore the total anesthesia time is longer, especially the anhepatic phase, because there are more graft vessels to be reconstructed before reperfusion. Overall the anesthetic management in terms of blood transfusion, fluid administration, sodium bicarbonate, calcium supplement, and the number of patients requiring fractional diluted noradrenaline support for maintenance of acceptable hemodynamic were not much different between the 2 groups.

Ergothioneine and melatonin attenuate oxidative stress and protect against learning and memory deficits in C57BL/6J mice treated with D-galactose.

Male C57BL/6J mice treated with D-galactose (DG) were used to examine the effects of ergothioneine (EGT), melatonin (MEL), or their combination (EGT+MEL) on learning and memory abilities. The mice were divided into five groups and injected subcutaneously with DG (0.3 mL of 1% DG/mouse) except for group 1 (normal controls). Group 3 was orally supplemented with EGT [0.5 mg/kg body weight (bw)], group 4 with MEL (10 mg/kg bw, p.o.), and group 5 with EGT+MEL. EGT and MEL were provided daily for 88 days, while DG was provided between days 7 to 56. Active avoidance task and Morris water-maze task were used to evaluate learning and memory abilities. DG treatment markedly increased escape latency and decreased the number of avoidance in the active avoidance test, whereas EGT and MEL alone significantly improved the performance. DG also impaired the learning and memory abilities in the water-maze task, and EGT and MEL alone also significantly improved the performance. EGT+MEL produced the strongest effects in both tasks. EGT and MEL alone markedly decreased ß-amyloid protein accumulation in the hippocampus and significantly inhibited lipid peroxidation and maintained glutathione/glutathione disulfide ratio and superoxide dismutase activity in brain tissues of DG-treated mice. MEL alone completely prevented the rise in brain acetylcholine esterase activity induced by DG, whereas EGT and EGT+MEL were only partially effective. Overall, EGT, MEL, and, in particular, the combination of EGT and MEL effectively protect against learning and memory deficits in C57BL/6J mice treated with DG, possibly through attenuation of oxidative damage.

First Report of a 16SrII-A Subgroup Phytoplasma Associated with Purple Coneflower (Echinacea purpurea) Witches'-Broom Disease in Taiwan.

Purple coneflower (Echinacea purpurea), widely grown as an ornamental and medicinal plant, is a perennial flowering plant that is native to eastern North America. In July 2011, symptoms indicative of phytoplasma disease, including floral virescence, phyllody, and witches'-broom (WB), were observed to be affecting plants in coneflower fields in Wufeng, Taichung City, Taiwan. Incidence of infected plants was estimated to be greater than 90% within a single field. Phytoplasmas previously associated with purple coneflower WB disease have all been classified as aster yellows group (16SrI) strains (GenBank Accession Nos. EU333395, AY394856, EU416172, and EF546778) except for pale purple coneflower (Echinacea pallida) WB in Australia, which was identified as a subgroup 16SrII-D member (2). Three diseased plants were uprooted and transplanted in a greenhouse for further study. Transmission electron microscopy revealed clusters of phytoplasma cells ranging from 170 to 490 nm in diameter in phloem sieve elements of virescent and phylloid flowers and stems from diseased plants. Comparable tissues from symptomless plants were devoid of phytoplasma. Total DNA was extracted from plant tissue samples (50 to 100 mg each) including stems, leaves, and flowers by a modified CTAB method (1) from three symptomatic plants as well as from three asymptomatic coneflower plants seedlings. Analyses by a nested PCR using universal primer pairs P1/P7 followed by R16F2n/R16R2 were performed to detect putative phytoplasma (2). Each primer pair amplified a single PCR product of either 1.8 or 1.2 kb, respectively, from diseased plant tissues only. The nested PCR products (1.2 kb) amplified from phylloid flowers of the three diseased plants were cloned separately and sequenced (GenBank Accession Nos. JN885460, JN885461, and JN885462). Blast analysis of the sequences revealed a 99.7 to 99.8% sequence identity with those of Echinacea WB phytoplasma strain EWB5 and EWB6 (GenBank Accession Nos. JF340076 and JF340080), which reportedly belonged to the 16SrII-D subgroup (2). Moreover, iPhyClassifier software (3) was used to perform sequence comparison and generate the virtual restriction fragment length polymorphism (RFLP) profile. The 16S rDNA sequences share a 99.4 to 99.5% similarity with that of the 'Candidatus Phytoplasma australasiae' reference strain (Y10097) and the RFLP patterns are identical to that of the 16SrII-A subgroup. Taken together, these results indicated that the phytoplasma infecting purple coneflower in Taiwan is a 'Ca. Phytoplasma australasiae'-related strain and belongs to the 16SrII-A subgroup. To our knowledge, this is the first report of a 16SrII-A subgroup phytoplasma causing WB disease on purple coneflower in Taiwan. The occurrence of phytoplasma on purple coneflower could have direct implication for the economically important ornamental, medicinal plant, and floral industry in Taiwan, especially to the growers and breeders that eagerly promote the purple coneflower industry. References: (1) T. M. Fulton et al. Plant Mol. Biol. Rep. 13:207, 1995. (2) T. L. Pearce et al. Plant Dis. 95:773, 2011. (3) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study.

UNLABELLED: The treatment of 300-mg/day isoflavones (aglycone equivalents) (172.5 mg genistein + 127.5 mg daidzein) for 2 years failed to prevent lumbar spine and total proximal femur bone mineral density (BMD) from declining as compared with the placebo group in a randomized, double-blind, two-arm designed study enrolling 431 postmenopausal women 45-65 years old. INTRODUCTION: This study evaluated the effects of soy isoflavones on bone metabolism in postmenopausal women. METHODS: Four hundred and thirty-one women, aged 45-65 years, orally consumed 300-mg/day isoflavones (aglycone equivalents) or a placebo for 2 years in a parallel group, randomized, double-blind, two-arm study. Each participant also ingested 600 mg of calcium and 125 IU of vitamin D(3) per day. The BMD of the lumbar spine and total proximal femur were measured using dual-energy X-ray absorptiometry at baseline and every half-year thereafter. Serum bone-specific alkaline phosphatase, urinary N-telopeptide of type 1 collagen/creatinine, and other safety assessments were examined regularly. RESULTS: Two hundred out of 217 subjects in the isoflavone group and 199 out of 214 cases in placebo group completed the treatment. Serum concentrations of isoflavone metabolites, genistein and daidzein, of the intervention group were remarkably elevated following intake of isoflavones (p < 0.001). However, differences in the mean percentage changes of BMD throughout the treatment period were not statistically significant (lumbar spine, p = 0.42; total femur, p = 0.39) between the isoflavone and placebo groups, according to the generalized estimating equation (GEE) method. A significant time trend of bone loss was observed at both sites as assessed by the GEE method following repeated measurement of BMD (p < 0.001). Differences in bone marker levels were not significant between the two treatment groups. CONCLUSION: Treatment with 300-mg/day isoflavones (aglycone equivalents) failed to prevent a decline in BMD in the lumbar spine or total femur compared with the placebo group.

A double-blind, placebo-controlled, randomized, multicenter study to investigate CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES Study).

UNLABELLED: Rationale Traditional Chinese Medications(TCM) have been reported to have beneficial effects in stroke patients, but were not rigorously evaluated by GCP standards. Aim This study tests the hypothesis that Neuroaid, a TCM widely used in China post-stroke, is superior to placebo in reducing neurological deficit and improving functional outcome in patients with acute cerebral infarction of an intermediate severity. Design This is a multicenter, randomised, double-blind, placebo-controlled study of Neuroaid in ischemic stroke patients with National Institute of Health Stroke Scale(NIHSS) 6-14 treated within 48 h of stroke onset. Neuroaid or placebo is taken (4 capsules) 3 times daily for 3 months. Treatments are assigned using block randomization, stratified for centers, via a central web-randomization system. With a power of 90% and two-sided test of 5% type I error, a sample size is 874. Allowing for a drop-out rate of up to 20%, 1100 individuals should be enrolled in this study. Study Outcomes The primary efficacy endpoint is the modified Rankin Scale(mRS) grades at 3 months. Secondary efficacy endpoints are the NIHSS score at 3 months; difference of NIHSS scores between baseline and 10 days, and between baseline and 3 months; difference of NIHSS sub-scores between baseline and 10 days, and between baseline and 3 months; mRS at 10 days, 1 month, and 3 months; Barthel index at 3 months; Mini Mental State Examination at 10 days and 3 months. Safety outcomes include complete blood count, renal and liver panels, and electrocardiogram. STUDY REGISTRATION: ClinicalTrials.gov identifier: NCT00554723.

Complications following combined transrectal ultrasound-guided prostate needle biopsies and transurethral resection of the prostate.

In order to evaluate safety and morbidity aspects of additional systematic prostate biopsies, we have conducted a retrospective review of patients who had undergone transurethral resection of the prostate (TUR-P) combined with additional systemic prostate needle biopsies at the Chang Gung Memorial Hospital. To this end, the records of 80 men presenting consecutively at our institution between February 2001 and January 2004 inclusively were examined. These 80 individuals included patients experiencing obstructive voiding symptoms and those featuring suspicious screening parameters, all of whom were to undergo transurethral resection of the prostate for symptomatic benign prostatic hyperplasia (BPH), all procedures being performed by a single surgeon. A total of 20 (25%) specimens were found to be positive for prostate cancer. Cancer was detected in the transrectal prostate biopsy specimen of 16 of 57 men (28%) who had not undergone a previous prostate biopsy, and for four of 23 (17%) who had undergone at least one previous (benign) biopsy. Mild complications associated with transurethral prostrate resection, such as hematuria and hemospermia, were reported frequently, featuring rates of 10% and 2.5%, respectively; more severe complications being noted far less frequently. Fever, usually of a low grade, was observed post-operatively for six (7.5%) patients, but a prompt return to normal temperature following antibiotic treatment for one day was revealed. Four (5%) patients remained admitted to the hospital for a prolonged period following surgery. A review of the literature concerning transrectal biopsies and TUR-P has shown that surgery-associated complication rates are slightly lower than was the case for our study. Additional systematic prostate biopsies for patients undergoing TUR-P would appear to be a relatively safe treatment procedure. Identification of risk factors for post-surgery complications might further improve the safety of the screening procedure.

Fatal pulmonary fibrosis associated with BCNU: the relative role of platelet-derived growth factor-B, insulin-like growth factor I, transforming growth factor-beta1 and cyclooxygenase-2.

Pulmonary fibrosis is a severe complication associated with bis-chloronitrosourea (BCNU) therapy. However, the pathogenetic mechanism has never been well investigated. We report here a 26-year-old female with diffuse large B-cell lymphoma who died of severe pulmonary fibrosis 81 days after the administration of high-dose BCNU (600 mg/m2). Thoracoscopic wedge resection of left upper lung performed 10 days before patient's death showed severe pulmonary fibrosis with prominent hyperplasia of alveolar macrophages and type II pneumocytes. We further used immunohistochemistry (IHC) to examine the relative role of platelet-derived growth factor-B (PDGF-B), insulin-like growth factor I (IGF-I), transforming growth factor-beta1 (TGF-beta1) and cyclooxygenase-2 (COX-2) in the pathogenesis of BCNU-related pulmonary fibrosis. Strong expressions of PDGF-B and IGF-1 on alveolar macrophages and type II pneumocytes were clearly demonstrated, but in contrast, the expressions of TGF-beta1 and COX-2 were almost undetectable. In conclusion, pulmonary fibrosis can develop early and progress rapidly after the administration of high-dose BCNU. The markedly increased expression of fibrogenic factors PDGF-B and IGF-1 on hyperplastic alveolar macrophages and hyperplastic type II pneumocytes may play an important role in the fibrogenesis of this disease. These novel findings may offer specific therapeutic targets in the treatment of BCNU-associated pulmonary fibrosis.

Bioavailability and pharmacokinetic features of etoposide in childhood acute lymphoblastic leukemia patients.

The bioavailability and pharmacokinetic characteristics of etoposide were studied in 12 relapsed B-lineage acute lymphoblastic leukemia (ALL) patients after both intravenous (i.v.) infusion and oral administration. Following a 1 hour i.v. infusion of 50 mg/m2 etoposide, the elimination half-life ranged from 49.8 min to 509.4 min (mean +/- SD = 218.6 +/- 134.7 min), the MRT ranged from 71.8 to 734.9 min (mean +/- SD = 315.4 +/- 194.3 min) and the systemic clearance of etoposide ranged from 15.7 to 38.0 ml/min/m2 (mean +/- SD = 24.1 +/- 7.0 ml/min/m2). The AUC ranged from 2234.9 to 5427.0 microM.min) (mean +/- SD = 3827.8 +/- 1069.5 microM.min) and Vc ranged from 2026.9 to 13,505.2 ml/m2 (mean +/- SD = 6825.4 +/- 3278.5 ml/m2). The maximum plasma etoposide levels ranged from 6.0 to 28.4 microM (mean +/- SD = 13.6 +/- 6.3 microM). The bioavailability of oral etoposide was determined by comparing the AUC following i.v. infusion to the AUC following oral administration in the same patient. The overall bioavailability (mean +/- SD) was 60.6 +/- 22.4% (ranged from 17.6% to 91.2%). The elimination half-life following oral administration (mean +/- SD) was 209.8 +/- 196.3 min (ranged from 51.0 to 794.2 min). The time required to reach the maximum plasma etoposide concentration was 145.4 +/- 118.7 min (ranged from 23.7 to 396.9 min). To our knowledge, this is the first report concerning the bioavailability of etoposide in pediatric leukemia patients. All of the other pharmacokinetic properties of etoposide in pediatric B-lineage ALL leukemia patients reported here were similar to those described previously.

The role of age and salivation in acid clearance in symptomatic patients with gastro-oesophageal reflux disease.

BACKGROUND: Cisapride has been shown to have not only prokinetic effects, but also salivary stimulating effects. Both of these mechanisms play an important role in the acid clearance of the oesophagus. AIM: To access the efficacy of cisapride in facilitating acid clearance in patients with symptomatic gastro-oesophageal reflux disease. METHODS: Fifteen older adults and 15 younger adults with symptomatic gastro-oesophageal reflux disease completed the study. The acid clearance test was accomplished by infusing 15 mL of 0.1 N HCl into the distal oesophagus, and the number of swallows was determined to achieve an oesophageal pH of 4.0. This was accomplished under baseline conditions and salivary stimulation with a peppermint lozenge. After 1 week of treatment with cisapride (10 mg, q.d.s.), the acid clearance test was repeated. RESULTS: The lozenge produced a significant decrease in the number of swallows compared to baseline in both groups (P < 0.01). There was a significant decrease in the number of swallows after the treatment with cisapride compared to baseline in both groups (P < 0.01). No significant difference was found in the number of swallows when comparing cisapride with lozenge. CONCLUSIONS: Cholinergic stimulation of salivation is an effective means of facilitating oesophageal acid clearance. Drugs, such as 5 hydroxytriptamine (5-HT)4-receptor agonists, should be considered as potentially important compounds in the treatment of gastro-oesophageal reflux disease.

Metaplastic carcinoma of the breast: analysis of eight Asian patients with special emphasis on two unusual cases presenting with inflammatory-type breast cancer.

Metaplastic carcinoma of the breast is a rare form of breast cancer and has an uncertain prognostic significance. Cases from Asian countries have never been reported in the English literature. Between 1983 and 1998, we encountered 8 cases in our institution. There were 7 women and one man with a median age of 52.5 (37-73) years. Pathologic diagnosis included three poorly-differentiated adenosquamous carcinomas, two adenocarcinomas with spindle cell metaplasia, two matrix-producing carcinomas and one carcinosarcoma. Estrogen receptor was positive in 2 (25%) patients. Local recurrence or distant metastasis developed in 3 patients within one year of initial treatment. With a mean follow-up of 81 months (range, 19-183 months), 5 patients were disease-free at the time of this report. Interestingly, two of our patients had presented with huge-sized inflammatory breast cancer and were refractory to neo-adjuvant chemotherapy, but enjoyed an unexpected long disease-free survival after mastectomy. Although the clinical course of our patients appeared in general similar to that of the Western series, the two patients with inflammatory breast carcinoma ran a very unusual course, which may deserve further characterization.

Preliminary acute and subchronic toxicity studies of GLG-V-13, a novel class III antiarrhythmic agent, in mice.

The acute and subchronic toxic effects of GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate, CAS 155029-33-7), a novel class III with some class Ib antiarrhythmic activity, were investigated in mice. The estimated LD50 for GLG-V-13 given orally were 419 mg/kg for male mice and 383 mg/kg for female mice, respectively. The acute toxic signs appeared to be of the central nervous system in origin. Four groups of mice (15 per sex, group and dose) were fed daily with diets containing GLG-V-13 for 90 consecutive days. The equivalent daily doses were 0, 22, 50 and 121 mg/kg/day and 0, 27, 60 and 136 mg/kg/day for male and female mice, respectively. All of the mice survived. Food consumption was decreased. However, mean body weight and body weight gain were not significantly changed. Gross pathological changes, especially in the lungs and liver, were found in the middle and high dose groups. Consistent increased mean corpuscular hemoglobin concentration and decreased mean corpuscular hemoglobin were observed in all dose groups. Hepatocellular necrosis was found in both male and female mice treated with the drug and was dose-dependent. Marked vacuolation of the X zone in the adrenal gland with mild to moderate deposition of ceroid pigments (brown degeneration) was observed in female mice. Lesions in the kidneys and adrenal glands may be a possible reason for changes in serum sodium and potassium ions concentrations leading to an increase in water intake. A significant reduction in cholesterol in the high dose group may be a favorable pharmacological effect of GLG-V-13. The data from the 90-day subchronic toxicity studies indicate that GLG-V-13 appears to have limited systemic toxicity potential.

Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history.

Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betel inflorescence, which contains 15 mg/g safrole, is a unique ingredient of BQ in Taiwan. Chewing such prepared BQ may contribute to safrole exposure in human beings (420 microM safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a (32)P-post-labeling method, we have found a high frequency of safrole-like DNA adducts in BQ-associated OSCC (77%, 23/30) and non-cancerous matched tissue (NCMT) (97%, 29/30). This was in contrast to the absence (< 1/10(9) nucleotides) of such adducts in all of non-BQ-associated OSCC and their paired NCMT (P < 0.001). Six of seven OSF also exhibited the same safrole-like DNA adduct. The DNA adduct levels in OSF and NCMT were significantly higher than in OSCC (P < 0.05). Using co-chromatography and rechromatography techniques, we further demonstrated that these adducts were identical to synthetic safrole-dGMP adducts as well as DNA adducts from 1'-hydroxysafrole-treated HepG2 cells. These results suggest that safrole forms stable safrole-DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis.

Synthesis, characterization and preclinical formulation of a dual-action phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07) with potent anti-HIV and spermicidal activities.

In a systematic effort to develop a microbicide contraceptive capable of preventing transmission of human immunodeficiency virus (HIV), as well as providing fertility control, we have previously identified novel phenyl phosphate derivatives of zidovudine (ZDV) with 5-halo 6-alkoxy substitutions in the thymine ring and halo substitution in the phenyl moiety respectively. Here, we describe the synthesis, characterization, and successful preclinical formulation of our lead compound, 5-bromo-6-methoxy-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate (WHI-07), which exhibits potent anti-HIV and sperm immobilizing activities. The anti-HIV activity of WHI-07 was tested by measuring viral p24 antigen production and reverse transcriptase activity as markers of viral replication in HIV-1 infected human peripheral blood mononuclear cells (PBMC). WHI-07 inhibited replication of HIV in a concentration-dependent fashion with nanomolar IC50 values. The effects of WHI-07 on human sperm motion kinematics were analysed by computer-assisted sperm analysis (CASA), and its effects on sperm membrane integrity were examined by confocal laser scanning microscopy (CLSM), and high-resolution low-voltage scanning electron microscopy (HR-LVSEM). WHI-07 caused cessation of sperm motility in a concentration- and time-dependent fashion. The in-vitro cytotoxicities of WHI-07 and nonoxynol-9 (N-9) were compared using normal human ectocervical and endocervical epithelial cells by the MTT cell viability assay. Unlike N-9, WHI-07 had no effect upon sperm plasma and acrosomal membrane integrity. N-9 was cytotoxic to normal human ectocervical and endocervical cells at spermicidal doses, whereas WHI-07 was selectively spermicidal. The in-vivo vaginal absorption and vaginal toxicity of 2% gel-microemulsion of WHI-07 was studied in the rabbit model. The sperm immobilizing activity of WHI-07 was 18-fold more potent than that of N-9. Over a 10 day period, there was no irritation or local toxicity to the vaginal epithelia or systemic absorption of WHI-07. Therefore, as a potent anti-HIV agent with spermicidal activity, and lack of mucosal toxicity, WHI-07 may have the clinical potential to become the active ingredient of a vaginal contraceptive for women who are at high risk for acquiring HIV by heterosexual vaginal transmission.

Characterization of residual lignin after SO(2)-catalyzed steam explosion and enzymatic hydrolysis of Eucalyptus viminalis wood chips.

The lignin component found in both water insoluble (WI) and water and alkali insoluble (WIA) fractions derived from SO(2)-impregnated steam-exploded eucalyptus chips (SEE) was isolated and characterized. Dioxane lignins with a sugar content lower than 2% (w/w) were obtained after each material was treated with commercial cellulases. The C9 formulas of both SEE-WI and SEE-WIA dioxane lignins were C(9)H(6.83)N(0.04)O(2.24)(OCH(3))(1.21)(OH(aro))(0.56)(OH(ali))(0. 77) and C(9)H(8.65)N(0.29)O(1.97)(OCH(3))(0.90)(OH(aro))(0. 46)(OH(ali))(1.02), respectively. The weight-average molecular weight (M(w)) of the SEE-WI lignin corresponded to 3.85 kDa, whereas the SEE-WIA lignin had an M(w) of 3.66 kDa for the same polydispersity of 2.4. The SEE-WIA lignin was shown to be more thermally stable than the SEE-WI lignin, requiring temperatures in the range of 520 degrees C for complete degradation. FTIR and (1)H NMR analyses of both untreated and peracetylated lignin fractions showed that (a) the alkali insoluble lignin contained a relatively higher degree of substitution in aromatic rings per C9 unit and that (b) alkaline extraction removed lignin fragments containing appreciable amounts of phenolic hydroxyl groups.

High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy.

BACKGROUND: In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS: To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS: Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P < 0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P < 0.01, log rank test). CONCLUSIONS: The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

Role of oxidative DNA damage in hydroxychavicol-induced genotoxicity.

Chewing betel quid has been linked to the development of oral cancer. In Taiwan, fresh Piper betle inflorescence is uniquely added to betel quid, and hydroxychavicol is the major phenolic components of P.betle inflorescence. In this study, we tested the mutagenic potential of hydroxychavicol in Salmonella typhimurium TA97, TA98, TA100 and TA102 with and without Aroclor-1254 induced S9 fraction. The results showed that hydroxychavicol was positive in S.typhimurium TA102 without metabolic activation. This increase in revertants was partially inhibited by catalase and superoxide dismutase. In Chinese hamster ovary (CHO-K1) cells, hydroxychavicol induced chromosome aberrations in a dose-dependent manner (10-50 microM) and the majority were chromosome-type aberrations. Hydroxychavicol also significantly increased the frequency of micronuclei in CHO-K1 cells up to 3-fold at a concentration of 40 microM. In addition, hydroxychavicol dose-dependently (0.1-20 microM) induced copper-dependent strand breaks in plasmid DNA. We further tested the oxidative DNA damage potential of hydroxychavicol by measuring 8-hydroxydeoxyguanosine (8-OH-dG) formation in CHO-K1 cells following an 18-h incubation and found that hydroxychavicol (6.25-100 microM) induced 8-OH-dG levels dose-dependently. The increase of 8-OH-dG formation was positively correlated (r = 0.79) with the hydroxychavicol-induced cytotoxicity. In conclusion, hydroxychavicol may exert its genotoxic potential through oxidative DNA damage.