Efficacy of prosultiamine treatment in patients with human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: results from an open-label clinical trial

Background: Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy characterized by motor dysfunction of the lower extremities and urinary disturbance. Immunomodulatory treatments are the main strategy for HAM/TSP, but several issues are associated with long-term treatment. We conducted a clinical trial with prosultiamine (which has apoptotic activity against HTLV-I-infected cells) as a novel therapy in HAM/TSP patients. Methods: We enrolled 24 HAM/TSP patients in this open-label clinical trial. Prosultiamine (300 mg, orally) was administered once daily for 12 weeks. We monitored changes in the motor function of the lower extremities and urinary function as well as copy numbers of the HTLV-I provirus in peripheral blood mononuclear cells (PBMCs). Results: Improvement in the motor function of the lower extremities based on a reduction in spasticity (for example, decrease in time required for walking and descending a flight of stairs) was observed. In an urodynamic study (UDS), bladder capacity and detrusor pressure and then maximum flow rate increased significantly. Detrusor overactivity and detrusor-sphincter dyssynergia improved in 68.8% and 45.5% of patients observed at pretreatment, respectively. Improvement in UDS corresponded with improvements in the score of nocturia-quality of life questionnaire. HTLV-I proviral copy numbers in PBMCs decreased significantly (approximately 15.4%) compared with pretreatment levels.Conclusions: These data suggest that prosultiamine can safely improve motor dysfunction of the lower extremities and urinary disturbance as well as reduce HTLV-I provirus levels in peripheral blood. It therefore has potential as a new therapeutic tool for HAM/TSP patients.Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000005969. Please see related commentary: http://www.biomedcentral.com/1741-7015/11/183

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of an Introduced Phytoene Synthase Gene Expression on Carotenoid Biosynthesis in the Marine Diatom Phaeodactylum tricornutum

Carotenoids exert beneficial effects on human health through their excellent antioxidant activity. To increase carotenoid productivity in the marine Pennales Phaeodactylum tricornutum, we genetically engineered the phytoene synthase gene (psy) to improve expression because RNA-sequencing analysis has suggested that the expression level of psy is lower than other enzyme-encoding genes that are involved in the carotenoid biosynthetic pathway. We isolated psy from P. tricornutum, and this gene was fused with the enhanced green fluorescent protein gene to detect psy expression. After transformation using the microparticle bombardment technique, we obtained several P. tricornutum transformants and confirmed psy expression in their plastids. We investigated the amounts of PSY mRNA and carotenoids, such as fucoxanthin and β-carotene, at different growth phases. The introduction of psy increased the fucoxanthin content of a transformants by approximately 1.45-fold relative to the levels in the wild-type diatom. However, some transformants failed to show a significant increase in the carotenoid content relative to that of the wild-type diatom. We also found that the amount of PSY mRNA at log phase might contribute to the increase in carotenoids in the transformants at stationary phase

C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin

Background Amrubicin hydrochloride (AMR) is a key agent for lung cancer. NADPH quinone oxidoreductase 1 (NQO1) metabolizes the quinone structures contained in both amrubicin (AMR) and amrubicinol (AMR-OH). We hypothesized that NQO 1 C609T polymorphism may affect AMR-related pharmacokinetics and clinical outcomes. Methods Patients received AMR doses of 30 or 40 mg/m 2 /day on days 1–3. Plasma sampling was performed 24 hours after the first and third AMR injections. Concentrations of AMR and AMR-OH were determined by HPLC and the NQO 1 C609T polymorphism was assayed by RT-PCR. Results A total of 35 patients were enrolled. At a dose of 40 mg/m 2 , the T/T genotype exhibited a tendency toward a relationship with decrease concentrations of AMR-OH on days 2 and 4. The genotype also showed a significant decrease of hematological toxicities ( P < 0.05). Conclusions NQO 1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities