Effective procedure to develop alternative annotations of bacterial tRNA genes by means of deductive inference on the basis of characteristic tandems of tRNA genes

In a series of analysis of genomic DNA sequences, we have established an induction-deduction method to dig up hidden tRNA and rRNA genes from bacterial genome DNA sequences by means of a concept of a characteristic tRNA-gene tandem we have ldeveloped, and are accumulating information on positions of putative tRNA and rRNA genes to be proposed as alternative annotations to the DDBJ/GenBank/EMBL Database. We have searched the DNA sequences near the existing tRNA genes as golcondas for tRNA genes, and found mord than fifty genes, e.g. tRNA-Ser and tRNA-Met in [AB013377], and 5S rRNAs in [AE014192], [AE017000], and others. A part of miserable states of the Database was partly introduced, and it is discussd how such status will be disso1ved. In addition, we proposed some ideas to maintain and improve the DDBJ/GenBank/EMBL database

Rapid diagnosis of drug intoxication using novel NAGINATA TM gas chromatography/mass spectrometry software

In Japan, not only the classical stimulant, methamphetamine, but also a wide variety of illicit drugs and designer drugs are abused by juveniles. It is, however, difficult to screen these drugs in human urine due to the poor availability of high-quality standards. Therefore, it is important to develop a screening method that does not require the use of standard compounds. Furthermore, if we can obtain approximate drug concentrations in biological fluids by the first screening procedure, the subsequent treatment of the patient and forensic diagnosis can be carried out more rapidly and exact quantitative analysis performed more efficiently. We have devised a rapid screening method for the simultaneous semi-quantitative analysis of 30 abused drugs using gas chromatography/mass spectrometry (GC/MS) with a retention time locking technique. Based on this method, an 'abused drugs database' was constructed including retention time (RT), qualifier ion/target ion (QT) percentage and calibration curve (values of slope and intercept) using the novel GC/MS software, NAGINATA TM . We compared the analytical results obtained by this method using the constructed database with those from conventional methods in six forensic cases. The number of confirmed drugs and concentrations obtained by the established method was comparable with that obtained by conventional methods. We found a significant improvement in the time for data analysis, and qualitative and quantitative information about each drug was obtained without using standards. Therefore, this new screening procedure using NAGINATA TM has potential for the rapid identification of poisoning and should be useful in clinical and forensic toxicological analyses

Successful pregnancy in renal transplant recipients.

Three cases of successful pregnancies in renal transplant recipients who had undergone transplantation in the Okayama University Medical School Hospital are reported. Two of the women had received an organ from a living relative and one woman received a cadaveric organ graft. These patients, aged 28-37 at the time of the delivery, had received their transplants 2-5 years prior to their conception. The periods of gestation ranged between 35 and 40 weeks. The weight of the babies at birth ranged from 2,380g to 2,500g and the apgar score at 1 min was 8 or 9. None of the infants showed any congenital abnormalities. Lower-segment cesarean section was performed in all of three cases. Serum creatinine levels, an indicator of renal graft function, did not deteriorate during the pregnancy or after delivery. Although further work is needed to solve problems regarding pregnancy in renal transplant recipients, these results encouraged us to meet their hope for a baby.</p

Restraint-Induced Expression of Endoplasmic Reticulum Stress-Related Genes in the Mouse Brain

ABSTRACT Depression is a significant public health concern but its pathology remains unclear. Previously, increases in an end

Overall survival and objective response in advanced unresectable hepatocellular carcinoma: A subanalysis of the REFLECT study

Background & aims: Validated surrogate endpoints for overall survival (OS) are important for expediting the clinical study and drug-development processes. Herein, we aimed to validate objective response as an independent predictor of OS in individuals with unresectable hepatocellular carcinoma (HCC) receiving systemic anti-angiogenic therapy. Methods: We investigated the association between objective response (investigator-assessed mRECIST, independent radiologic review [IRR] mRECIST and RECIST v1.1) and OS in REFLECT, a phase III study of lenvatinib vs. sorafenib. We conducted landmark analyses (Simon-Makuch) of OS by objective response at 2, 4, and 6 months after randomization. Results: Median OS was 21.6 months (95% CI 18.6-24.5) for responders (investigator-assessed mRECIST) vs. 11.9 months (95% CI 10.7-12.8) for non-responders (hazard ratio [HR] 0.61; 95% CI 0.49-0.76; p <0.001). Objective response by IRR per mRECIST and RECIST v1.1 supported the association with OS (HR 0.61; 95% CI 0.51-0.72; p <0.001 and HR 0.50; 95% CI 0.39-0.65; p <0.001, respectively). OS was significantly prolonged for responders vs. non-responders (investigator-assessed mRECIST) at the 2-month (HR 0.61; 95% CI 0.49-0.76; p <0.001), 4-month (HR 0.63; 95% CI 0.51-0.80; p <0.001), and 6-month (HR 0.68; 95% CI 0.54-0.86; p <0.001) landmarks. Results were similar when assessed by IRR, with both mRECIST and RECIST v1.1. An exploratory multivariate Cox regression analysis identified objective response by investigator-assessed mRECIST (HR 0.55; 95% CI 0.44-0.68; p <0.0001) and IRR-assessed RECIST v1.1 (HR 0.49; 95% CI, 0.38-0.64; p <0.0001) as independent predictors of OS in individuals with unresectable HCC. Conclusions: Objective response was an independent predictor of OS in individuals with unresectable HCC in REFLECT; additional studies are needed to confirm surrogacy. Participants achieving a complete or partial response by mRECIST or RECIST v1.1 had significantly longer survival vs. those with stable/progressive/non-evaluable disease

Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

Background: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1–3, FGF receptors 1–4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. Methods: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions. Patients were randomly assigned (1:1) via an interactive voice–web response system—with region; macroscopic portal vein invasion, extrahepatic spread, or both; Eastern Cooperative Oncology Group performance status; and bodyweight as stratification factors—to receive oral lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight &lt;60 kg) or sorafenib 400 mg twice-daily in 28-day cycles. The primary endpoint was overall survival, measured from the date of randomisation until the date of death from any cause. The efficacy analysis followed the intention-to-treat principle, and only patients who received treatment were included in the safety analysis. The non-inferiority margin was set at 1·08. The trial is registered with ClinicalTrials.gov, number NCT01761266. Findings: Between March 1, 2013 and July 30, 2015, 1492 patients were recruited. 954 eligible patients were randomly assigned to lenvatinib (n=478) or sorafenib (n=476). Median survival time for lenvatinib of 13·6 months (95% CI 12·1–14·9) was non-inferior to sorafenib (12·3 months, 10·4–13·9; hazard ratio 0·92, 95% CI 0·79–1·06), meeting criteria for non-inferiority. The most common any-grade adverse events were hypertension (201 [42%]), diarrhoea (184 [39%]), decreased appetite (162 [34%]), and decreased weight (147 [31%]) for lenvatinib, and palmar-plantar erythrodysaesthesia (249 [52%]), diarrhoea (220 [46%]), hypertension (144 [30%]), and decreased appetite (127 [27%]) for sorafenib. Interpretation: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. The safety and tolerability profiles of lenvatinib were consistent with those previously observed