Ability of plant pathogenic fungi Gibberella fujikuroi and Fusarium commune to react with airborne methyl jasmonate.

The pathogenic fungi Gibberella fujikuroi and Fusarium commune produce jasmonic acid. The application of volatile deuterium-labeled methyl jasmonate increased the amount of nonlabeled JA present in G. fujikuroi and F. commune. These results indicate that the fungi have the ability to react with airborne methyl jasmonate in a manner similar to a plant.

DNA markers linked to Pga1, an adzuki bean gene that confers resistance to Cadophora gregata race 1.

Brown stem rot (BSR) caused by Cadophora gregata f. sp. adzukicola (syn. Phialophora gregata) is a serious soilborne disease of adzuki bean (Vigna angularis) in Japan. Cultivation of resistant cultivars is the most effective disease control method, therefore the selection of resistant lines is a priority for breeders. BSR-resistant adzuki bean lines have been screened in pathogen-infected fields. However, field selection using the pathogen and artificial inoculation methods is time-consuming and labor-intensive. In the present study, we used 105 F3 lines derived from a cross between a BSR-resistant cultivar 'Syumari' and a susceptible cultivar 'Buchishoryukei-1' for BSR inoculation tests. Amplified fragment-length polymorphism (AFLP) analyses with 1024 primer sets revealed that six fragments were polymorphic between resistance and susceptible bulked groups. Five DNA markers (Pg77, Pg118, Pg138, Pg139 and Pg126) were developed from the nucleotide sequences of polymorphic AFLP markers and their flanking regions. Pg118, which was derived from E-ACT/M-ACT-118, was tightly linked to the resistance gene Pga1 and was converted into a codominant marker for its easier use in marker-assisted selection for adzuki bean BSR resistance. Finally, the applicability of the developed markers for BSR resistance was tested on 32 adzuki bean accessions or cultivars.

Diagnostic sensitivity of ¹8fluorodeoxyglucose positron emission tomography for detecting synchronous multiple primary cancers in head and neck cancer patients.

We assessed the sensitivity of positron emission tomography (PET) for detecting synchronous multiple primary cancers, particularly synchronous esophageal cancers in head and neck cancer patients. We retrospectively reviewed 230 head and neck cancer patients. All the patients routinely underwent the following examinations: urinalysis, occult blood, tumor marker detection [squamous cell carcinoma (SCC), cytokeratin fragment (CYFRA), and carcinoembryonic antigen (CEA)], esophagogastroduodenoscopy, colonoscopy (when CEA was high or occult blood was positive), abdominal ultrasonography, plain chest computed tomography (CT), and PET. Bronchoscopy was performed when CT revealed lung shadow of central region. Synchronous multiple primary cancers were detected in 42 (18.2%) patients. The diagnostic sensitivity of PET for synchronous primary cancers was as follows: esophagus, 7.6% (1/13); stomach, 25.0% (2/8); lung, 66.7% (4/6); head and neck, 75.0% (3/4); colon, 0% (0/1); kidney, 0% (0/1); and subcutaneous, 100% (1/1). The sensitivity of PET for detecting synchronous esophageal cancers is low because these are early-stage cancers (almost stage 0-I). Therefore, it is necessary to perform esophagogastroduodenoscopy for detecting synchronous esophageal cancers. PET is an important additional tool for detecting synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous head and neck cancer and lung cancer is high. But PET has the limitation of sensitivity for synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous esophageal cancer is very low.

Common Spear Rot of Oil Palm in Indonesia.

Common spear rot (CSR), which is also known as crown disease, was first reported in Indonesia in the 1920s. It has caused considerable losses in young oil palm plantings, and yet the pathogenic agent has remained elusive. Symptomatic spear leaves were collected from oil palm plantations and farm plots in South Sumatra, North Sumatra, and Bangka-Belitung, Indonesia. Of the 14 different fungi isolated, Fusarium incarnatum, F. solani, an undescribed Fusarium sp., and Ceratocystis paradoxa were isolated most frequently from diseased leaf tissue. F. incarnatum and the undescribed Fusarium sp. were also frequently isolated from healthy leaf tissue, along with Pestalotiopsis microspora and Curvularia affinis. Ceratocystis paradoxa was never isolated from healthy leaf tissue. Koch's postulate experiments showed that C. paradoxa was able to infect wounded oil palm leaves causing a symptom of extensive rotting similar to that found in the field. Although isolated less frequently and less virulent than C. paradoxa, F. sacchari was also capable of causing lesions on succulent wounded, inoculated leaves. For both C. paradoxa and F. sacchari, the disease severity index was greater when the oil palm leaves appeared to have more succulent growth. Likewise, other Fusarium species and other nonfusarial fungi that were usually not pathogenic were weakly virulent on palms with more succulent growth. These findings confirm that C. paradoxa is one pathogen that is associated with CSR of oil palm in Indonesia.

New Sources of Resistance to Cadophora gregata f. sp. adzukicola and Fusarium oxysporum f. sp. adzukicola in Vigna spp.

Adzuki bean brown stem rot (BSR), caused by Cadophora gregata f. sp. adzukicola, and adzuki bean Fusarium wilt (AFW), caused by Fusarium oxysporum f. sp. adzukicola, are serious problems in Hokkaido, Japan, and have been managed using cultivars with multiple resistance. However, a limited number of adzuki bean varieties are resistant to these pathogens because of the frequent appearance of new races; thus, new sources of resistance have been sought in related Vigna spp., particularly in the section Angulares to which adzuki bean belongs. An analysis of selected Vigna accessions (JP81231 to JP235420) conserved in the Genebank of the National Institute of Agrobiological Sciences, Tsukuba, Japan, revealed wide variation in resistance spectra and resistance combinations, and eight disease response groups (A to H) were identified. Four of eight were newly detected response groups, suggesting the existence of novel resistance genes. Of 252 accessions from 26 species, 28 accessions in Vigna angularis var. nipponensis, V. hirtella, V. minima, and V. tenuicaulis (section Angulares) from group D, which were cross-compatible with adzuki bean, are expected to be potential sources of multiple resistance genes. They were resistant to all races of BSR and AFW pathogens examined.

Gene status of head and neck squamous cell carcinoma cell lines and cetuximab-mediated biological activities.

Cetuximab is a chimeric IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR). Cetuximab binds to EGFR and prevents phosphorylation of EGFR. Moreover, preclinical results have shown the ability of cetuximab to induce either complement-mediated tumor cell killing (CDC) or antibody-dependent cell-mediated-cytotoxicity (ADCC). We previously reported mutation in EGFR regarding head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, we analyzed the same 16 HNSCC cell lines for mutations in KRAS, PIK3CA, BRAF and PTEN. Furthermore, we evaluated cetuximab-mediated biological activities (antiproliferative effect by the MTT assay and ADCC) regarding these cell lines. Mutations in PIK3CA and PTEN were observed in two cell lines (2/16, 12.5%), but no mutation was observed in KRAS and BRAF. The antiproliferative effect of cetuximab by the MTT assay was not strong, and no correlation was observed between the antiproliferative effect of cetuximab and mutations in EGFR, KRAS, PIK3CA, BRAF and PTEN in these cell lines. Therefore, the mutation status of EGFR and downstream molecules were not useful for predicting the antitumor effects of cetuximab on HNSCC. Cetuximab-mediated ADCC was observed in these cell lines and might have been influenced by the expression of EGFR. Therefore, cetuximab-mediated ADCC seems to be an important part of the antitumor mechanisms of cetuximab and the expression levels of EGFR might influence the antitumor activity of cetuximab. Therefore, besides the antiproliferative effect of cetuximab by the MTT assay, it appeared important to evaluate cetuximab-mediated ADCC as well as EGFR expression in HNSCC cells.

Quantification of Phytophthora infestans population densities and their changes in potato field soil using real-time PCR.

Tuber infection of Phytophthora infestans often occurs at harvest. However, it is difficult to accurately estimate the population densities of P. infestans in soil, especially Japanese soil. In the present study, P. infestans DNA was extracted from soil samples using a modified CTAB-bead method and quantified using real-time PCR to accurately, rapidly and easily estimate the P. infestans population densities in upland soils in Japan. P. infestans was well quantified in eleven types of soil samples, including nine types of upland soils in Japan, that were artificially inoculated with a zoosporangia suspension. The amounts of P. infestans DNA estimated by the real-time PCR were proportional to the inoculum densities. In the non-controlled experimental potato field, P. infestans population densities in soil corresponded to the development of symptoms and were correlated with the number of lesions on the potato foliage. These results imply that the proposed real-time PCR assay is suitable for the estimation or monitoring of P. infestans population densities in upland soils in Japan. The population densities at the ridge bottoms were larger than those at any other location in commercial potato fields. These results were similar to those of a previous report using a bioassay. Moreover, a correlation between DNA quantity and inoculum potential was observed. In conclusion, the real-time PCR assay developed in this study is suitable for indirect estimation of the inoculum potential of P. infestans.

Soluble form of ephrinB2 inhibits xenograft growth of squamous cell carcinoma of the head and neck.

The ephB4-ephrinB2 system plays an important role in the interaction of tumor cells with endothelial cells (ECs). To assess the role of ephB4 in the in vivo growth of head and neck squamous cell carcinoma (HNSCC), we used ephrinB2-Fc, a fusion protein consisting of the extracellular domain of ephrin-B2 and the Fc portion of human IgG1, as the soluble ligand for ephB4. EphrinB2-Fc injection into HNSCC xenografted mice significantly suppressed xenograft growth, accompanied by a decrease in vessel cross-sectional area, but there was no change in vessel number. EphrinB2-Fc injection also induced the formation of mature blood vessels rich in alpha-smooth muscle actin positive pericytes in the xenograft tissue. In vitro assays revealed that ephrinB2-Fc inhibited the proliferation of human umbilical vein ECs (HUVECs) but not tumor cells. Furthermore, real-time quantitative RT-PCR showed that ephrinB2-Fc down-regulated matrix metalloproteinase-2 mRNA expression in HUVECs and vascular endothelial growth factor-A in tumor cells. These data suggest that treatment with ephrinB2-Fc, the soluble ligand of ephB4, inhibited the growth of HNSCC through vessel maturation/stabilization, preventing leakiness and endothelial sprout formation.

Tonsillectomy plus steroid pulse therapy is the most effective treatment in adult patients with C-Grade I IgA nephropathy, and the weight of the extracted palatine tonsils and Yamamoto scale have no significant correlation with the effects of this treatment.

OBJECTIVE: We studied patients who underwent tonsillectomy plus steroid pulse therapy (TSP) for immunoglobulin A nephropathy (IgAN), in order to investigate the clinical factors associated with a positive response to this treatment. METHODS: We analyzed 118 IgAN patients who underwent TSP. We collected patients' data retrospectively, including age, sex, blood pressure, onset of IgAN, pathological findings of a renal biopsy, serum concentration of creatinine, estimated glomerular filtration rate, serum concentration of protein, urinary protein, hematuria, past history of tonsillitis, the Yamamoto scale, the weight and pathological findings of the extracted palatine tonsils, and the presence or absence of anti-platelet drugs and renin-angiotensin system inhibitors (RAS-I) usage. This study included participants who were over 18 years of age, had undergone tonsillectomy within three months of steroid pulse therapy administered thrice, in whom renal biopsy was performed within a year before treatment, and with follow-up period of over 3 years. Clinical remission (CR) of urinary abnormalities was defined as remission of both proteinuria and hematuria: three consecutive negative results over a 6-month period, with a urinary sediment red blood cell count of <5/HPF, and a proteinuria qualitative reaction of (-) to (±). RESULTS: The CR rate of all cases was 56.8% and statistical significance was observed with respect to the C-Grade (P = 0.0003, P = 0.028) using both univariate and multivariate analysis. The CR rate of C-Grade І (73.4%) patients was significantly higher than that of C-Grade II patients (39.0%; P = 0.0004) and C-Grade III patients (30.8%; P = 0.003). We analyzed clinical factors in each C-Grade patient. No statistical significance was observed with respect to any of the factors using univariate analysis in C-Grade I patients. The weight of the extracted palatine tonsils and Yamamoto scale showed no statistical significance in every analysis. Fibrosis or hyalinization of the stroma of the palatine tonsils showed statistical significance (P = 0.026) only in the univariate analysis of C-Grade III patients. However, the patient number of C-Grade III was small. CONCLUSION: Our results indicate that TSP is mostly effective in patients with of C-Grade I IgAN and that the C-Grade reflects the clinical indication for TSP. The weight of the extracted palatine tonsils and Yamamoto scale did not show obvious correlations with the clinical effect of TSP.

Anti-tumor effects of telomelysin for head and neck squamous cell carcinoma.

Telomelysin is a telomerase-specific replication-competent adenovirus with telomerase reverse transcriptase (hTERT) promoter, which has shown strong anti-tumor effects on a variety of human cancer cells. Human head and neck squamous cell carcinoma (HNSCC) cell lines and a murine HNSCC (NR-S1) model were used to investigate whether telomelysin (OBP-301) had a therapeutic efficacy for HNSCC. We examined the cell killing effects of telomelysin and the induction of tumor cell apoptosis by telomelysin in vitro. Based on these data, we examined whether telomelysin therapy produced therapeutic benefits in vivo. The results demonstrated that the treatment of telomelysin led to significant tumor regression on the side with subcutaneous NR-S1 tumor. We first confirmed the direct anti-tumor effect of intratumoral telomelysin injections in a murine HNSCC model. Further analyses of the augmented anti-tumor effects revealed that telomelysin increased the source of tumor antigens for immune cells, resulting in the induction of CD4+ and CD8+ T cells responsible for the in vivo tumor regression of treated and untreated tumors. Subsequently, an elevated IFN-gamma production of spleen cells was observed in mice treated with telomelysin. These results raise the possibility that telomelysin enhances the immune response in addition to its direct tumor cell killing activity. These findings suggest that telomelysin is a potent agent for the treatment of HNSCC patients with multiple metastases.

Antitumor effect of gefitinib on head and neck squamous cell carcinoma enhanced by trastuzumab.

The overexpression of EGFR and/or HER-2 is associated with tumor cell resistance to chemotherapy, radiotherapy, disease progression and poor prognosis in patients with a variety of malignant tumors. Treatment combining the EGFR-targeting drug, gefitinib (ZD1839, Iressa) with the HER-2-targeting drug, trastuzumab (Herceptin) has been reported to improve therapeutic efficacy in patients with breast cancer. The purpose of this study was to examine the antitumor effect of this combination on head and neck squamous cell carcinoma (HNSCC) in vitro. Cell proliferation was inhibited significantly in two cell lines. Although IC50 of gefitinib alone against some cell lines was not reached, it was achieved after being combined with trastuzumab. Furthermore, IC50 was lower for the combination than for gefitinib alone in several cell lines. These results suggest that the combination may improve efficacy against HNSCC.

Enhanced virulence of Fusarium species associated with spear rot of oil palm following recovery from osmotic stress.

Fusarium spp., which are common inhabitants of oil palm leaves, are weak pathogens of common spear rot (CSR). We investigated the influence of osmotic stress on the growth, virulence, and activity of cell wall-degrading enzymes of CSR fungi, using potato dextrose agar (PDA) supplemented with KCl or sucrose (hyperosmotic medium). Hyperosmotic stress significantly inhibited mycelial growth, but growth rapidly recovered when mycelia were transferred to control medium. When inoculated into oil palm spear leaflets, Fusarium sp., and F. incarnatum precultured on 1.0 and 1.5 M KCl-hyperosmotic medium induced lesions that were two to four times larger than those in non-stressed cultures, suggesting enhanced virulence of the weak pathogens. Lesion size was not greatly affected in hyperosmotic cultures of moderately virulent F. sacchari. No activity of pectin lyase was detected in liquid cultures of the Fusarium isolates. All isolates except F. incarnatum BT48 secreted polygalacturonase (PG), which was active in both liquid cultures and inoculated leaves. Significantly increased PG activity (5-32-fold) was observed on leaves inoculated with hyperosmotic cultures of Fusarium sp. and F. sacchari. These findings suggest that Fusarium sp., F. incarnatum, and F. sacchari exhibit an adaptive physiological plasticity to hyperosmotic stress that results in enhanced virulence.

Patients Over 60 Years of Age Have Poor Prognosis in Facial Nerve Decompression Surgery with Preserved Ossicular Chain.

OBJECTIVE: We report our retrospective study of the recovery rate of auditory ossicles preserved facial nerve decompression surgery via the transmastoid approach in cases of both an electroneurography score of < 10% and a Yanagihara score of ≤8 in Bell's palsy and Ramsay Hunt syndrome. MATERIALS AND METHODS: We retrospectively reviewed 47 patients who we were able to follow-up for more than 6 months following the onset of palsy. The recovery rate was defined by the Japan Society for Facial Nerve Research or the Yanagihara score. RESULTS: Twelve months after palsy onset, the recovery rate was 48.8% (20/41) for all patients, 65.2% (15/23) for patients with Bell's palsy, and 27.8% (5/18) for patients with Ramsay Hunt syndrome. Comparing the clinical efficacy of surgical treatment at 12 months after palsy onset, we observed a statistically significant effect of age. Comparing the Yanagihara scores of patients aged < 60 years with those of patients aged ≥60 years revealed that patients aged ≥60 years had significant poor prognosis, particularly in patients with Ramsay Hunt syndrome, which showed a very low recovery rate (14.3%). We also analyzed six other factors, but none showed statistical significance. CONCLUSION: The clinical efficacy of surgical treatment of Ramsay Hunt syndrome was inferior to that of Bell's palsy, which is consistent with previous reports. There was a statistically significant difference in the Yanagihara score between patients aged < 60 years and those aged ≥60 years. Particularly, patients with Ramsay Hunt syndrome aged ≥60 years have a very low recovery rate.

Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis: The minor axis of the sialolith is a regulative factor for the removal of sialoliths in the hilum of the submandibular gland using sialendoscopy alone.

OBJECTIVE: To assess the general guidelines for the removal of sialoliths for submandibular gland sialolithiasis using sialendoscopy alone. METHODS: We analyzed 61 sialoliths treated using sialendoscopy in 42 patients with submandibular gland sialolithiasis. We evaluated the submandibular gland sialoliths and divided each case based upon the location: the Wharton's duct or the hilum. We measured the major and minor axes of the sialoliths using a soft tissue computed-tomography (CT) scan and evaluated the removal rate of the sialoliths using sialendoscopy alone. RESULTS: The removal rate of the sialoliths in the Wharton's duct (52.6%) was significantly higher than that in the hilum of the submandibular gland (26.1%) (P=0.042). The minor axis was significantly correlated to the treatment outcome of sialendoscopy alone for all cases (P=0.030). A significant correlation was observed for cases involving the hilum of the submandibular gland and the measurement of the minor axes of the sialoliths for the treatment outcome of sialendoscopy alone (P=0.009). The major axis showed no correlation with the treatment outcomes of sialendoscopy alone. CONCLUSION: The measurement of the minor axes of the sialoliths with a soft tissue CT scan was correlated with treatment outcome of sialendoscopy alone for all cases, particularly sialoliths in the hilum. The easurement of the major axis showed no correlation with outcomes of sialendoscopy alone.

Diagnostic and treatment effects of sialendoscopy for patients with swelling of the parotid gland when sialoliths are undetected with computed tomography.

Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct. Balloon expansion of the duct was performed in these 2 patients and a steroid drug was injected into the duct in one patient. Complete remission was archived in one patient treated with sialendoscopy. Three patients had sialolithiasis. Microsialoliths and/or white floating matter was observed and removed using sialendoscopy. All patients experienced complete remission. In cases of Sjögren syndrome and recurrent parotitis, sialendoscopic surgery was performed, but the symptoms showed no improvement. For patients with microsialoliths, sialendoscopy may be most useful for diagnosis and treatment when the sialoliths are not detected with CT imaging. At present, sialendoscopic surgery have limitation in the treatment of Stensen's duct stenosis and may similarly have limitation in the treatment of Sjögren's syndrome and recurrent parotitis.

The landmark for removal of sialoliths using sialendoscopy alone in parotid gland sialolithiasis.

OBJECTIVE: To assess the general guidelines for removal of sialoliths in parotid gland sialolithiasis using sialendoscopy alone. METHODS: We analyzed 34 sialoliths treated using sialendoscopy in 26 patients with parotid gland sialolithiasis. We divided the Stensen's duct and parotid gland into for parts using computed tomography findings: (A) front of the masseter, (B) anterior and lateral to the center (anterolateral) of the masseter, (C) posterior and lateral to the center (posterolateral) of the masseter, (D) behind of the masseter. The location and size of each sialolith was assessed. RESULTS: The removal rates of sialoliths in the different locations by sialendoscopy alone were as follows: front of the masseter, 68.8%; anterolateral of the masseter, 60.0%; posterolateral of the masseter, 0%; and behind of the masseter, 33.3%. The removal rate using sialendoscopy alone was significantly higher in the sections anterior to the center of the masseter than in those posterior to the center of the masseter (66.7% [14/21] vs. 20.0% [2/10]; P=0.019). The size of the sialolith was not correlated to the removal rate by sialendoscopy alone. CONCLUSION: Sialoliths of the parotid gland located in positions anterior to the center of the masseter are significantly easier to remove by sialendoscopy alone. The center of the masseter is a general landmark for removal of sialoliths from the parotid gland using sialendoscopy alone. The size of the sialolith is not correlated with removal, except rare huge sialoliths.

Concurrent chemoradiotherapy for T4 patients with hypopharyngeal and laryngeal squamous cell carcinomas.

OBJECTIVES: Concurrent chemoradiotherapy (CCR) was given for the previously untreated T4 hypopharyngeal and laryngeal squamous cell carcinoma patients and the response and survival rates were evaluated. PATIENTS AND METHODS: A total of 23 patients, namely, 15 for hypopharynx and 8 for larynx were eligible. These patients were given cisplatin and 5-fluorouracil based chemotherapeutic regimens with conventional radiotherapy for a total dose of 66.6-70.2 Gy. RESULTS: Ten out of the 15 hypopharyngeal carcinoma patients and 4 out of the 8 laryngeal carcinoma patients showed a complete response at the primary sites. The 5-year disease-specific survival rate was 59.4% in all the patients, 51.9% in the hypopharyngeal carcinoma patients, and 71.0% in the laryngeal patients. Seven out of the 12 resectable hypopharyngeal carcinoma patients and 4 out of 8 laryngeal carcinoma patients were able to do without total laryngectomy. CONCLUSIONS: Based on these results, the survival rate in the hypopharyngeal and laryngeal T4 carcinoma patients treated by CCR seems to be satisfactory and the possibility of organ preservation for the advanced patients is indicated.

[Association with relative nocturnal polyuria using BNP (brain natriuretic peptide) in eldely patients with nocturia].

OBJECTIVE: In addition to overactive bladder (OAB) and sleep disorders (disturbance of additional sleep induction), nocturnal polyuria has been reported as an etiology of nocturia in elderly people. To investigate the influence of heart function on nocturnal polyuria in elderly people, we examined the association with nocturnal polyuria using brain natoriuretic peptide (BNP), which are useful for evaluating the prognosis of heart failure. PATIENTS AND METHODS: The patients were 128 patients (92 males, 36 females) who were treated for nocturia in Kohsei general hospital and other relative hospital between October 2002 and September 2005. We measured BNP levels at physical examination. Simultaneously, the patients were instructed to write a frequency volume chart (FVC) for 4 days. 24-hour urine volume, Daytime urine volume, nocturnal (sleep) urine volume, nocturnal polyuria index (NPi) were calculated from FVC. The association was examined. However, alphal-blockers or anticholinergic agents that had been prescribed to treat urination disorders were continuously administered. RESULTS: Overall, the mean BNP level was high, 46.3+/-39.6 pg/ml. The mean 24-hour urine volume was 1,555+/- 458 ml. The mean daytime urine volume was 935+/-322 ml. The mean nocturnal urine volume was 624+/-251 ml. The mean nocturnal urine volume rate was high, 40.1 - 10.5%. However, there was a close association between BNP and the 24-hour urine volume (p = 0.0215), the daytime urine volume (p = 0.0004), the NPi (p = 0.0003). The daytime urine volume decreased with the BNP level. The NPi increased with the BNP level. Patients were divided into 2 groups, a group with a BNP level less than 50 pg/ml and a group with a BNP level of 50 pg/ml or more. In the group with a BNP level less than 50 pg/ml, the nocturnal urine volume rate was 38.14+/-10.07%. In the group with a BNP level of 50 pg/ml or more, the rate was significantly higher (43.97+/-10.48%, p<0.0029). CONCLUSIONS: These results suggest that many elderly patients latently have mild heart failure, and that relative nocturnal polyuria reduces cardiac load. Therefore, in patients with a high BNP level, administration of antidiuretic hormone to decrease nocturnal urine volume is risky. Administration of diuretics during the afternoon or evening may be safer.

Elucidation of the biosynthetic pathway of cis-jasmone in Lasiodiplodia theobromae.

In plants, cis-jasmone (CJ) is synthesized from α-linolenic acid (LA) via two biosynthetic pathways using jasmonic acid (JA) and iso-12-oxo-phytodienoic acid (iso-OPDA) as key intermediates. However, there have been no reports documenting CJ production by microorganisms. In the present study, the production of fungal-derived CJ by Lasiodiplodia theobromae was observed for the first time, although this production was not observed for Botrytis cinerea, Verticillium longisporum, Fusarium oxysporum, Gibberella fujikuroi, and Cochliobolus heterostrophus. To investigate the biosynthetic pathway of CJ in L. theobromae, administration experiments using [18,18,18-2H3, 17,17-2H2]LA (LA-d5), [18,18,18-2H3, 17,17-2H2]12-oxo-phytodienoic acid (cis-OPDA-d5), [5',5',5'-2H3, 4',4'-2H2, 3'-2H1]OPC 8:0 (OPC8-d6), [5',5',5'-2H3, 4',4'-2H2, 3'-2H1]OPC 6:0 (OPC6-d6), [5',5',5'-2H3, 4',4'-2H2, 3'-2H1]OPC 4:0 (OPC4-d6), and [11,11-2H2, 10,10-2H2, 8,8-2H2, 2,2-2H2]methyl iso-12-oxo-phytodienoate (iso-MeOPDA-d8) were carried out, revealing that the fungus produced CJ through a single biosynthetic pathway via iso-OPDA. Interestingly, it was suggested that the previously predicted decarboxylation step of 3,7-didehydroJA to afford CJ might not be involved in CJ biosynthesis in L. theobromae.

[Change of creatinine clearance rate in accordance with aging in Japanese patients with head and neck cancer].

Most of the head and neck tumors are squamous cell carcinomas (SCCs), which are relatively sensitive to chemotherapeutic agents. Cis-platinum (CDDP), 5-fluorouracil and taxanes are widely used worldwide for SCCs, and CDDP is the most common agent. Renal toxicity is a well-known adverse effect of CDDP, and adequate pre and post-hydration or combined administration of neutralizing agents is performed during CDDP injection. Before the CDDP administration, we have to evaluate renal function of the patients using creatinine clearance rate (Ccr). In Japan, CDDP at the dose of 60-70 mg/m(2)/day is administered in cases with over 65 ml/min/1.73 m(2) of Ccr, whereas in cases under 60 ml/min/1.73 m(2), we use other drugs, e.g., carboplatin, to prevent the renal dysfunction followed by chemotherapy. In other countries, the dose of CDDP is 70-100 mg/m(2)/day, and the discrepancy is based on the poor renal function of Japanese. We calculated Ccrs of 107 head and neck cancer patients since January, 2004 to August, 2005, and evaluated renal function before any treatment. Ccr was decreased in proportion to aging. At the age of fifties, 43.5% of the patients indicated lower Ccr than 65 ml/min/1.73 m(2): sixties, 45.7%; seventies, 50.0%; and eighties, 85.7%. In the United States, the average glomerular filtration rate of over 70 year-old healthy people is estimated as 75 ml/min/ 1.73 m(2), and it is considered sufficient kidney function for the administration of CDDP at the dose of 70-100 mg/ m(2)/day. The incident rate of end-stage renal disease is 1.3 times higher in the United States than in Japan. The incident rate of diabetes, which is the main cause of renal dysfunction, is almost the same in both countries. Though the reason is unclear, it is the fact that the renal function of Japanese decreases quickly in accordance with aging.