Sakurako Uozu

A Rice Brassinosteroid-Deficient Mutant, ebisu dwarf (d2), Is Caused by a Loss of Function of a New Member of Cytochrome P450

We characterized a rice dwarf mutant, ebisu dwarf (d2). It showed the pleiotropic abnormal phenotype similar to that of the rice brassinosteroid (BR)-insensitive mutant, d61. The dwarf phenotype of d2 was rescued by exogenous brassinolide treatment. The accumulation profile of BR intermediates in the d2 mutants confirmed that these plants are deficient in late BR biosynthesis. We cloned the D2 gene by map-based cloning. The D2 gene encoded a novel cytochrome P450 classified in CYP90D that is highly similar to the reported BR synthesis enzymes. Introduction of the wild D2 gene into d2-1 rescued the abnormal phenotype of the mutants. In feeding experiments, 3-dehydro-6-deoxoteasterone, 3-dehydroteasterone, and brassinolide effectively caused the lamina joints of the d2 plants to bend, whereas more upstream compounds did not cause bending. Based on these results, we conclude that D2/CYP90D2 catalyzes the steps from 6-deoxoteasterone to 3-dehydro-6-deoxoteasterone and from teasterone to 3-dehydroteasterone in the late BR biosynthesis pathway.

A simple method of bronchial occlusion with silicone spigots (Endobronchial Watanabe Spigot; EWS®) using a curette.

Background: Bronchial occlusion with an Endobronchial Watanabe Spigot (EWS) has been shown to be useful in managing prolonged bronchopleural fistulas and intractable hemoptysis. EWS bronchial occlusion using a curette is less technically demanding. This retrospective study evaluated the clinical utility and simplicity of this method. Methods: A total of 18 consecutive patients (15 men, 3 women, aged 47–85 years) who underwent bronchial occlusion using an EWS from April 2012 to August 2014 were evaluated. The method involves sticking the tip of a curette into an EWS to the first joint, allowing it to be turned in any direction or at any angle. The time required to occlude the target bronchus was measured on routinely recorded digital videos. Other parameters evaluated included success rates, complications, and clinical outcomes. Results: Of the 18 patients, 11 underwent bronchial occlusion for intractable pneumothorax, 5 for postoperative bronchopleural fistula, two for intractable empyema, and one for hemoptysis. Each patient required 1–7 EWSs (median 4). Target bronchi included the right upper (n = 8), left upper (n = 5), right lower (n = 2), left lower (n = 2), and right middle (n = 1) bronchi. The success rate of EWS insertion into the target bronchus was 100%. Time per EWS occlusion ranged from 65–528 sec (median 158.5 sec). Of the 62 insertions, 36 (58.1%) were completed within 3 min, and 58 (93.5%) within 5 min. Successful outcomes were observed in 15 (83.3%) of the 18 patients. Conclusions: EWS bronchial occlusion using a curette is a simple method for managing intractable bronchopleural fistulas in daily clinical settings.

Pharmacokinetics of Gefitinib in a Patient with Non-Small Cell Lung Cancer Undergoing Continuous Ambulatory Peritoneal Dialysis

A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure and who had undergone right upper lobectomy for lung adenocarcinoma (pT2aN0M0) 2 years ago was admitted for recurrence of lung cancer presenting as multiple brain metastases. An epidermal growth factor receptor mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746-A750) in exon 19. After whole-brain radiotherapy, we started daily administration of 250 mg gefitinib under the continuation of CAPD and performed a pharmacokinetic analysis. We speculated that the plasma concentration of gefitinib reached the steady state at least by day 16 after the start of gefitinib (626.6 ng/ml at trough level). On day 46, the plasma concentration was 538.4 ng/ml at trough level and the concentration in the peritoneal dialysis fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the pharmacokinetics of gefitinib. During gefitinib therapy, there were no significant adverse events except for grade 2 diarrhea. Gefitinib could be safely administered to a patient undergoing CAPD.

Gender Differences in the Clinical Features of Sleep Apnea Syndrome

Objective Sleep apnea syndrome is more prevalent among men than women and is frequently accompanied by metabolic syndrome (MetS). However, gender differences in the effect of sleep-disordered breathing (SDB) leading to the risk of MetS remain unclear. The aim of our study was to investigate the clinical characteristics of SDB in women and the differential influence of SDB on MetS between genders. Methods In a single-center retrospective study, we compared the data of 1,809 consecutive SDB patients by gender to clarify the characteristics of sleep disorders in women. We also compared the prevalence of MetS and its related abnormalities by gender. A logistic regression analysis was used to determine the contributory factors for MetS. Results The mean age and proportion of patients over 50 years of age were higher in women than in men. SDB was milder in women than in men according to polysomnography findings. Elevated Hemoglobin A1c levels and hyperlipidemia were less frequent in women than in men. The MetS prevalence was similar in women and men (30.0% vs. 35.2%). A logistic regression analysis showed that the apnea-hypopnea index (AHI) was an independent risk factor for MetS in both genders, but that female gender was independently associated with a decreased prevalence of MetS and its related abnormalities. Conclusion Female SDB patients tend to be older with milder apnea and sleepiness than male SDB patients. A higher AHI is a significant risk factor for MetS in both genders, although female gender is an independent inhibitory factor for developing MetS in SDB patients.

Increased airway hyperresponsiveness to adenosine in patients with aspirin intolerant asthma

Age (mean ± SD) 42.6 ± 17.0 42.1 ± 14.9 n.s. Male 4 5 n.s. Atopy (þ/ ) 6/3 12/6 n.s. Severity (mild/moderate) 5/7 7/10 n.s. FVC (ml, mean ± SD) 3006 ± 586 3085 ± 722 n.s. FEV1.0 (ml, mean ± SD) 2430 ± 537 2365 ± 602 n.s. FEV1.0% (%, mean ± SD) 81.4 ± 9.2 77.2 ± 6.8 n.s. %FEV1.0 (%, mean ± SD) 90.3 ± 14.3 85.5 ± 13.3 n.s. WBC (/ml, mean ± SD) 6300 ± 1500 6900 ± 2200 n.s. Eosinophil (%, mean ± SD) 9.2 ± 6.3 6.5 ± 2.9 n.s. IgE (U/ml, mean ± SD) 285.5 ± 272.4 421.3 ± 404.9 n.s. Therapy n.s. ICS (mg, mean ± SD) 420 ± 261 360 ± 214 n.s. LABA (n) 6 5 n.s. Theophylline (n) 9 13 n.s. Dear Editor,

Feasibility of tissue re-biopsy in non-small cell lung cancers resistant to previous epidermal growth factor receptor tyrosine kinase inhibitor therapies

BackgroundWhen epidermal growth factor receptor (EGFR) gene mutation-positive non-small cell lung cancer (NSCLC) acquires resistance to the initial tyrosine kinase inhibitor (TKI) treatment, reassessing the tumor DNA by re-biopsy is essential for further treatment selection. However, the process of TKI-sensitive tumor re-progression and whether re-biopsy is possible in all cases of acquired resistance to EGFR-TKI remain unclear.MethodsWe retrospectively analyzed data from 69 consecutive patients with EGFR gene mutation-positive advanced NSCLC who had been treated with EGFR-TKI and exhibited disease relapse after initial disease remission. The relapsing lesions were identified at the time of RECIST-progressive disease (PD) and clinical-PD (when the attending physician judged the patient as clinically relapsing and stopped EGFR-TKI therapy). We determined the potential re-biopsy methods for each relapsing lesion and evaluated their feasibility according to difficulty and invasiveness criteria as follows: category A, accessible by conventional biopsy techniques; category B, difficult (but possible) to biopsy and accessible with invasive methods; and category C, extremely difficult to biopsy or inaccessible without using highly invasive methods, including surgical biopsy.ResultsThe total feasibility rate of re-biopsy (category A or B) was 68% at RECIST-PD and 84% at clinical-PD, and the most common accessible relapsing lesions were primary tumors at RECIST-PD and pleural effusion at clinical-PD. All relapsing lesions at primary sites (categories A and B) were assessed as having the potential for re-biopsy. However, re-biopsy for metastasis was assessed as difficult in a substantial proportion of the study population (42 and 20% category C at RECIST-PD and clinical-PD, respectively).ConclusionsRe-biopsy of relapsing disease is feasible in many cases, although it may present difficulties in cases with, e.g., metastatic relapsing lesions. To facilitate treatment strategies in NSCLC patients with relapse after EGFR-TKI therapy, re-biopsy should be standardized with the use of simpler and more reliable methods.