Search

Clinical practice guidelines emphasize that optimal pharmacotherapy, including beta-blockers (BB), is a prerequisite before receiving cardiac resynchronization therapy (CRT) in eligible patients with heart failure (HF). However, the optimal dose of BB before CRT implantation cannot be tolerated in a number of patients. Sixty-three consecutive patients who underwent CRT in 2006-2013 were retrospectively investigated. Before receiving CRT, BB could not be introduced in 20 patients (32 %); the daily carvedilol-equivalent dose in other 43 patients was 5.6 ± 7.0 mg because of significant HF and bradycardia. After receiving CRT, BB could be introduced in almost all patients (n = 61, 97 %), and the daily BB dose increased from 5.6 ± 7.0 to 13.2 ± 7.8 mg (P

Leaf mold of tomato is caused by the biotrophic fungus Cladosporium fulvum which complies with the gene-for-gene system. The disease was first reported in Japan in the 1920s and has since been frequently observed. Initially only race 0 isolates were reported, but since the consecutive introduction of resistance genes Cf-2, Cf-4, Cf-5 and Cf-9 new races have evolved. Here we first determined the virulence spectrum of 133 C. fulvum isolates collected from 22 prefectures in Japan, and subsequently sequenced the avirulence (Avr) genes Avr2, Avr4, Avr4E, Avr5 and Avr9 to determine the molecular basis of overcoming Cf genes. Twelve races of C. fulvum with a different virulence spectrum were identified, of which races 9, 2.9, 4.9, 4.5.9 and 4.9.11 occur only in Japan. The Avr genes in many of these races contain unique mutations not observed in races identified elsewhere in the world including (i) frameshift mutations and (ii) transposon insertions in Avr2, (iii) point mutations in Avr4 and Avr4E, and (iv) deletions of Avr4E, Avr5 and Avr9. New races have developed by selection pressure imposed by consecutive introductions of Cf-2, Cf-4, Cf-5 and Cf-9 genes in commercially grown tomato cultivars. Our study shows that molecular variations to adapt to different Cf genes in an isolated C. fulvum population in Japan are novel but overall follow similar patterns as those observed in populations from other parts of the world. Implications for breeding of more durable C. fulvum resistant varieties are discussed.

A chitosan-degrading bacterium, isolated from field soil that had been amended with chitin, was identified as Sphingobacterium multivorum KST-009 on the basis of its bacteriological characteristics. The extracellular chitosanase (SM1) secreted by KST-009 was a 34-kDa protein and could be purified through ammonium sulfate precipitation, gel permeation column chromatography and SDS polyacrylamide gel electrophoresis. A chitosanase gene (csnSM1) was isolated from genomic DNA of the bacteria, and the entire nucleotide sequence of the gene and the partial N-terminal amino acid sequence of the purified SM1 were determined. The csnSM1 gene was found to encode 383 amino acids, 72 N-terminal amino acid residues were processed to produce the mature enzyme during the secretion process. Germinated microconidia of four formae speciales (lycopersici, radicis-lycopersici, melonis, and fragariae ) of Fusarium oxysporum were treated with SM1. Chitosanase treatment caused morphological changes, such as swelling of hyphal cells or indistinctness of hyphal cell tips and cessation or reduction of mycelial elongation.

Leaf mold symptoms were found on tomato varieties carrying the Cf-9 resistance gene against Passalora fulva, the causal agent of leaf mold, in Japan in 2008. Disease symptoms and morphological characteristics of the isolates were similar to those of P. fulva. After inoculating a set of tomato differentials with the isolates, all isolates were identified as race 2.9 of P. fulva, previously unreported.

Cladosporium fulvum is a biotrophic fungal pathogen that causes leaf mould of tomato. Analysis of its genome suggested a high potential for production of secondary metabolites (SM), which might be harmful to plants and animals. Here, we have analysed in detail the predicted SM gene clusters of C. fulvum employing phylogenetic and comparative genomic approaches. Expression of the SM core genes was measured by RT-qrtPCR and produced SMs were determined by LC-MS and NMR analyses. The genome of C. fulvum contains six gene clusters that are conserved in other fungal species, which have undergone rearrangements and gene losses associated with the presence of transposable elements. Although being a biotroph, C. fulvum has the potential to produce elsinochrome and cercosporin toxins. However, the corresponding core genes are not expressed during infection of tomato. Only two core genes, PKS6 and NPS9, show high expression in planta, but both are significantly down regulated during colonization of the mesophyll tissue. In vitro SM profiling detected only one major compound that was identified as cladofulvin. PKS6 is likely involved in the production of this pigment because it is the only core gene significantly expressed under these conditions. Cladofulvin does not cause necrosis on Solanaceae plants and does not show any antimicrobial activity. In contrast to other biotrophic fungi that have a reduced SM production capacity, our studies on C. fulvum suggest that down-regulation of SM biosynthetic pathways might represent another mechanism associated with a biotrophic lifestyle.

A 56-year-old man was admitted to our hospital because of increasing chest discomfort and abnormal chest shadow. Computed tomography (CT) of the chest revealed an anterior mediastinal mass, pleural dissemination and lung metastasis. Percutaneus needle biopsy guided by CT showed that the mass was advanced thymic cancer (stage IV b according to the classification proposed by Masaoka). After failure of combination chemotherapy of cisplatin, vincristine, doxorubicin and etoposide (CODE), he received 4 cycles of carboplatin plus paclitaxel and then achieved confirmed stable disease. In terms of toxicity profile, grade 4 anemia, grade 2 leucopenia and neutropenia were observed, and particularly non-severe toxicity was not observed in terms of non-hematologic toxicity. Carboplatin plus paclitaxel can be an active agent against pretreated thymic cancer.

The filamentous fungus Fusarium oxysporum is a soil-borne parasite that causes vascular wilts in a wide variety of crops by directly penetrating roots and colonizing the vascular tissue. In previous work, we generated the non-pathogenic mutant B137 of the melon wilt pathogen F. oxysporum f. sp. melonis by using restriction enzyme-mediated integration (REMI) mutagenesis. Molecular characterization of B137 revealed that this mutant has a single-copy plasmid insertion in a gene, designated FOW2, which encodes a putative transcription regulator belonging to the Zn(II)2Cys6 family. The REMI mutant B137 and other FOW2-targeted mutants completely lost pathogenicity, but were not impaired in vegetative growth and conidiation in cultures. Microscopic observation of infection behaviours of green fluorescent protein (GFP)-marked wild-type and mutant strains revealed that the mutants were defective in their abilities to invade roots and colonize plant tissues. FOW2 is conserved in F. oxysporum pathogens that infect different plants. The FOW2-targeted mutants of the tomato wilt pathogen F. oxysporum f. sp. lycopersici also lost pathogenicity. Nuclear localization of Fow2 was verified using strains expressing Fow2-GFP and GFP-Fow2 fusion proteins. These data strongly suggest that FOW2 encodes a transcription regulator controlling the plant infection capability of F. oxysporum pathogens.

strain pattern. Results: LVRR was observed in 38 patients (55%). D QRS voltage, D QRS duration, and D QTc duration were significantly smaller in the positive LVRR group (P!0.001, P50.042 and P50.010, respectively). The percentage of STT normalization was higher in the positive LVRR group (P50.005). Multivariate analysis revealed that D QRS voltage was a significant determinant of LVRR (odds ratio50.192, P!0.001). D QRS voltage was inversely related to the change of LVEF (R5-0.512, P!0.001) and LVDd (R5-0.559, P!0.001). In addition, Kaplan-Meier survival analysis indicated that D QRS voltage!-0.440 subgroup have a favorable prognosis (P50.001). Conclusion: The change of RV5+SV1 voltage in ECG is associated with LVRR in DCM.

Fusarium oxysporum produces three kinds of asexual spores, microconidia, macroconidia, and chlamydospores. F. oxysporum produces microconidia and macroconidia in carboxymethyl cellulose-added liquid medium (CMCLM) and exhibits vegetative growth without conidiation in complete liquid medium (CLM). The cDNA libraries were constructed using mRNAs from CLM and CMCLM cultures. A total of 1288 and 1353 clones from CLM (vegetative growth) and CMCLM (conidiation) libraries, respectively, were sequenced, and 641 and 626 unique genes were identified. Of these unique genes, only 130 ( approximately 20%) were common in the two libraries, indicating different patterns of gene expression during vegetative growth and conidiation. The expression levels of 496 CMCLM-specific genes were compared during vegetative growth and conidiation by cDNA dot-blot differential hybridization and real-time quantitative PCR analyses, and 42 genes were identified to display >5-fold increases in mRNA abundance during conidiation. These genes provide ideal candidates for further studies directed at understanding fungal conidiogenesis and its molecular regulation.

Purpose: Although identification of left ventricular reverse remodeling (LVRR) has been demonstrated to have prognostic value for the stratification of long-term risk in cardiac patients, no studies have investigated the clinical significance of differences in the timing of LVRR detection to predict prognosis in patients with nonischemic dilated cardiomyopathy (NIDCM). Methods: We reviewed the institutional heart failure (HF) database records of 307 consecutive patients diagnosed with NIDCM from 1996 to 2011.Of all patients, we included 261 patients (85%) whose clinical data (including serial echocardiography) for more than 2 years was available. LVRR was defined as an absolute increase in LV ejection fraction ≥10% to a final value of ≥35% accompanied by a decrease in LV end-diastolic dimension of ≤10%. Patients were followed-up until death due to any cause, such as cardiovascular death, readmission for HF, or detection of major ventricular arrhythmia. Results: During the study period, in patients receiving tailored medical therapy, LVRR was found in 123 patients (49%). LVRR was an independent predictor of cardiac events by Cox proportional hazard analysis (risk ratio, =0.266; 95% confidence interval, 0.140-0.472; p

Purpose: Although experimental studies have demonstrated that tolvaptan (TLV), a selective vasopressin V2-receptor antagonist, induces free water clearance without increasing urine sodium, there are only few reports on its clinical efficacy concerning urodynamics in acute decompensated heart failure (ADHF) patients concomitant with conventional diuretic use in usual practice. Methods: 22 consecutive ADHF patients with volume overload despite using loop diuretics were treated with TLV for 7 days. We divided these patients into two groups, responder (R, ≥+42%) or non-responder (N