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In this study, 1,1-difluoroallenes underwent a regioselective [2+3] cycloaddition with nitrile oxides and imine oxides in the presence of a AuCl catalyst. ( E )-4-Alkylidene-5,5-difluoroisoxazolines and -isoxazolidines were obtained in regioselective and diastereoselective manners by employing aurated difluoroallylic cation intermediates. The synthesized 5,5-difluoroisoxazolines were readily aromatized through dehydrofluorination or allylic fluorine substitution to provide 5-fluoroisoxazoles.

A 78-year-old man with a prostate-specific antigen level of 10 ng/mL was referred to our hospital. Magnetic resonance imaging revealed a Prostate Imaging-Reporting and Data System category of 5 in the apex transition zone. Transrectal and transperineal prostate needle biopsies were performed at a total of 20 sites. A well-differentiated adenocarcinoma with a Gleason score of 3+3 was detected on the right peripheral zone of the biopsied specimen. There were no apparent metastases, and robot-assisted radical prostatectomy was performed (Lesion 1: 30 mm lesion with a Gleason score of 4+5, EPE1, RM1, ly0, v0, pn1, sv0 in the bilateral transitional zones; Lesion 2: 4 mm lesion with a Gleason score of 3+3, EPE0, RM0, ly0, v0, pn0, sv0 in the left peripheral zone). Lymph node metastasis was found in the separately submitted anterior prostatic fat tissue. Removal of the anterior prostatic fat tissue is a simple procedure and is considered useful for evaluating the stump, and in this hospital, the tissue is routinely submitted for pathological diagnosis. It is extremely unlikely that lymph nodes will be found in the anterior prostatic fat tissue, and it is even less likely that any lymph node in the tissue will contain lymph node metastases. We therefore report a case of incidental discovery of lymph node metastasis in the anterior prostatic fat tissue at our hospital.

Purpose: MRI-targeted biopsy has improved prostate biopsy yield. However, cost constraints have made it difficult for many institutions to implement the newer methods. We evaluated the performance of a low-cost cognitive-targeting biopsy protocol based on 1.5 T multiparametric MRI graded with Prostate Imaging Reporting and Data System (PI-RADS) version 2 to examine the role for these institutions moving forward., Methods: Retrospective analysis of 251 consecutive patients with prostate-specific antigen (PSA) under 50 who underwent MRI and subsequent prostate biopsy at a single facility. In addition to systematic biopsy, targeted cores were obtained with cognitive recognition under ultrasound. A control group of 267 consecutive patients with PSA under 50 biopsied without prior MRI was analyzed., Results: Prostate biopsy preceded by MRI had a significantly higher probability of detecting both prostate cancer (68.1% vs. 51.3%) and clinically significant prostate cancer (57.4% vs. 39.7%) (p values < 0.01). Combination of systematic and targeted biopsy outperformed either regimen alone. PSA density and PI-RADS score were identified as independent risk factors, and a proposed diagnostic model (PSA density ≥ 0.25 or PI-RADS score ≥ 4) showed sensitivity of 88.6%, specificity of 55%, PPV of 81.2%, NPV of 68.8%, and accuracy of 78.0%., Conclusions: Both pre-biopsy MRI and cognitive-targeted biopsy contributed to improvement of cancer yield. Future alterations of possible benefit included increasing target cores per lesion, and combining PI-RADS score and PSA density as indicators for biopsy. Similar protocols may represent an on-going role for lower volume centers in the diagnosis of prostate cancer.

We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We found that discolored waste nori with no commercial value, contains much higher level of porphyran than normal nori that is a sheeted food stuff prepared from P. yezoensis used in sushi. Chemical analyses revealed that mean molecular mass of the porphyran prepared from discolored nori (dc-porphyran) was much lower than that of the porphyran from normal nori (n-porphyran). Dc-porphyran showed slightly greater scavenging activity toward superoxide anion and hydroxyl radical than n-porphyran. Dc-porphyran inhibited nitric oxide (NO) production in LPS-stimulated RAW264.7 cells through preventing the expression of inducible NO synthase, whereas no such activity was observed in n-porphyran. Since acid-hydrolyzed n-porphyran showed the inhibitory activity on NO production from LPS-stimulated RAW264.7 cells, the molecular size of porphyran was suggested to be a critical factor for the activity. Dc-porphyran was separated into 4 fractions (F1-F4) on DEAE-chromatography, and F1 showed the highest inhibitory effect on NO production from LPS-stimulated RAW264.7 cells. Our results indicate that discolored waste nori is useful as a source of porphyran with even better bioactivities than porphyran from normal nori., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Alginate is an acidic linear polysaccharide with immune-modulating activities. In this study, we found that enzymatically digested alginate oligomer (AO) with various degrees of polymerization (DP; 2-5) induced a higher level of nitric oxide (NO) production in RAW264.7 cells than undigested alginate polymer (AP). Reverse transcription-polymerase chain reaction and western blot analyses revealed that the expression level of inducible NO synthase in AO-treated RAW264.7 cells was higher than that in AP-treated cells. AO induced nuclear translocation of nuclear factor (NF)-κB p65 subunit in RAW264.7 cells to a greater extent than AP. Although AO and AP induced similar extents of phosphorylation in three mitogen-activated protein (MAP) kinases, c-Jun N-terminal kinase inhibitor exhibited the most potent inhibitory effect on NO induction in AO- and AP-treated RAW264.7 cells, among three MAP kinase inhibitors that were tested.

The Japanese pharmaceutical market, the world's second largest, is traditionally renowned for the domination of patented drugs and the weakest generics share among major established economies. An in-depth observation of published evidence in Japanese/English language provided closer insight into current trends in Japanese domestic legislation and pharmaceutical market development. Recent governmental interventions have resulted in significant expansion of the generic medicines market size. Substantial savings due to generic substitution of patent-protected drugs have already been achieved and are likely to increase in future. Nationwide population aging threatening sustainable healthcare funding is contributing to the relevance of generic policy success. Serious long-term challenges to the modest Japanese generic manufacturing capacities will be posed by foreign pharmaceutical industries particularly the ones based in emerging BRIC economies.

We evaluated the antitumor activity of crude extract and ascophyllan prepared from Ascophyllum nodosum in sarcoma-180 solid tumor-bearing mice with continuous intraperitoneal (i.p.) administration at a dose of 50 mg/kg body weight/day or oral administration at a dose of 500 mg/kg body weight/day. Ascophyllan and crude extract administered via the oral route showed greater antitumor effects than via i.p. route, and the tumor sizes in mice treated with ascopyllan and crude extract were reduced by a mean of 68.7±6.8% and 42.4±24.8% by the oral route, and 41.4±16.1% and 13.6±20.6% by i.p. route compared to control mice. Splenic natural killer cell activity in the mice treated with ascophyllan and crude extract by i.p. route was significantly enhanced, while only a slight increase of this activity was observed in orally-treated mice. Furthermore, increase in spleen weight of tumor-bearing mice was slightly suppressed by oral administration of ascophyllan, whereas i.p. administration resulted in further enlargement. Analysis of serum cytokines revealed that oral treatment with ascophyllan resulted in significant increase of tumor necrosis factor-α and interleukin-12 levels. Since ascophyllan showed no direct cytotoxic effect on sarcoma-180 cells, orally-administered ascophyllan is suggested to exhibit its antitumor activity through the activation of the host immune system.

Solitary fibrous tumor (SFT) is a neoplasm of pleura and its occurrence in the retroperitoneal space is rare. We report a case of SFT of the adrenal gland associated with ipsilateral renal cell carcinoma (RCC) and angiomyolipoma (AML). A 48-year-old woman was referred to our hospital for a left renal AML. Computed tomography (CT) in our hospital showed a left adrenal mass (25 x 20 mm). Because the adrenal tumor was nonfunctioning, she was followed at outpatient clinic. Four years later, CT showed an increase in the left adrenal tumor size (42 x 30 mm) and a left RCC. Left adrenectomy and partial nephrectomy for RCC and AML were simultaneously performed. Histological examination revealed adrenal SFT and clear cell carcinoma and AML of the kidney. We present a brief review on histological characteristics of retroperitoneal SFT and its occurrence in the adrenal grand region.

Treatment of perylene bisimide (PBI) with various arylboronates in the presence of a ruthenium catalyst provides tetraarylated PBIs at 2,5,8,11-positions in good yields with perfect regioselectivity. The electronic nature of the introduced aryl substituents has a significant impact on their optical and electronic properties. This protocol has been applied to the synthesis of a water-soluble emissive PBI derivative.

To investigate the effect of incorporation of beta-alanine in alkylating N-methylpyrrole (Py)-N-methylimidazole (Im) polyamide, seco-CBI conjugates 2-8 were synthesized by an Fmoc solid-phase method and subsequent coupling with an alkylating moiety. DNA-alkylating activities of conjugates 2-8 were evaluated by high-resolution denaturing gel electrophoresis with 202-base pair (bp) DNA fragments. Alkylation by conjugates 2 and 3, which have antiparallel pairings of beta-alanine (beta) opposite beta (beta/beta) and Py/beta, occurred mainly at the adenine (A) of the matching sequences, 5'-AGCTCCA-3' (site 1) and 5'-AGCACCA-3' (site 3). However, conjugate 4, with beta/Py, did not show any DNA-alkylating activities. Similarly, conjugate 5, which possessed a Py/Py pair, weakly alkylated the matching sites at micromolar concentrations. Conjugates 6 and 7, which possessed beta/beta and Py/beta pairs, respectively, alkylated at the A of the matching sequences, 5'-ACTACCA-3' (site 2) and 5'-ACAACCA-3' (site 4). In contrast, conjugated 8, with a Py/Py pair, showed lower activity and less alkylated DNA at sites 2 and 4 with mismatched alkylation at site 1 at a higher concentration than that of 6 and 7. These results demonstrate that incorporation of beta-alanine is required for the sequence-specific alkylation by seco-CBI Py-Im conjugates with a seven-base pair sequence.

Highly regioselective and efficient borylation of a variety of porphyrins has been achieved by reaction with bis(pinacolato)diboron through C-H bond activation under iridium catalysis on the basis of the synthetic protocol developed by Miyaura, Hartwig, and Smith. A boryl group can be selectively introduced at sterically uncongested positions in the peripheral aryl groups of porphyrin substrates whose peripheral beta-positions are sterically hindered. Curiously, beta substituents adjacent to the aryl group to be borylated have unexpectedly large effects on the regioselectivity, because the iridium catalyst can discriminate between subtle steric differences. Chemoselective borylation was also achieved for several functionalized porphyrins. This borylation protocol can be applied to various monomeric and oligomeric functional porphyrins, hence offering an efficient route to elaborate multiporphyrin-based molecular constructs.

Objectives: To examine urinary parameters among normal individuals and patients with calcium oxalate (CaOx) stones after oral administration of potassium-sodium citrate (KNa-Cit) and magnesium oxide (MgO). Urinary citrate and magnesium have been known as the inhibitors of CaOx stone formation. Supplementation with potassium-magnesium citrate prevents the recurrence of CaOx stones., Methods: Twenty-five male volunteers aged 21 to 42 years without a history of urinary stones were given either KNa-Cit or MgO, or both. Fourteen patients with recurrent CaOx stones were also given both supplements, and 24-hour urine samples were collected to determine the urinary parameters., Results: The administration of both KNa-Cit and MgO to the normal individuals increased the excretion of citrate, magnesium, and potassium by 70.0%, 44.2%, and 50.0%, respectively. These parameters increased less when KNa-Cit or MgO was administered individually. After administration of both supplements to the patients with stones, the citrate, magnesium, and potassium levels increased by 62.1%, 63.3%, and 25.3%, respectively, and oxalate decreased by 66.5%. In both normal individuals and patients, the ion activity product index of CaOx decreased significantly more after administration of the combination than with either compound alone or before administration., Conclusion: The combination of KNa-Cit and MgO is more effective than either supplement alone in inhibiting the crystallization of CaOx stones. The combination may improve the urinary parameters of patients with stones accompanied by hypocitraturia and/or hypomagnesuria.

A novel technique of lidar for atmospheric gas detection by use of stimulated Raman gain spectroscopy without any tunable laser is proposed. Detection sensitivity and detectable range are estimated on the basis of the lidar equation for CO2, CH4, and H2 in the atmosphere. The feasibility study clearly shows that the technique has a potential for application to lidar and that, in addition, the construction of the system is simpler than those of traditional differential absorption lidars.

A new nonlinear Raman spectroscopy technique for trace-gas detection was proposed and demonstrated. The technique involved the use of a thermal-lens detection scheme to monitor thermal emission from the stimulated Raman process. We termed this technique thermal-lens Raman spectroscopy, and it was combined with a novel scheme involving a nonlinear Raman spectroscopy without a tunable laser. This technique was applied to detecting trace hydrogen molecules in the atmosphere by use of a pulsed Nd:YAG laser and a continuous-wave He-Ne probe laser. A detection limit of 9 parts in 10(6) was attained.

We have implemented a system for assisting experts in selecting MEDLINE records for database construction purposes. This system has two specific features: The first is a learning mechanism which extracts characteristics in the abstracts of MEDLINE records of interest as patterns. These patterns reflect selection decisions by experts and are used for screening the records. The second is a keyword recommendation system which assists and supplements experts' knowledge in unexpected cases. Combined with a conventional keyword-based information retrieval system, this system may provide an efficient and comfortable environment for MEDLINE record selection by experts. Some computational experiments are provided to prove that this idea is useful.

Steric interactions between methoxy and tert-butyl groups are the reason that 2 only exists as p-phenylenebis(N-tert-butylaminoxyl) B. The p-phenylenebis(N-tert-butylaminoxyl) 1 has the p-quinonediimine N,N'-dioxide structure Q in solution as well as in the crystalline state., (© 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)

Pyogenic sacro-iliitis (PS) is a rare disease in childhood. Three cases of PS are reported that were difficult to diagnose. Scintigraphy and magnetic resonance imaging (MRI) were useful for diagnosis. One patient suffered from an episode of relapse. Seventeen other cases of PS were reviewed in the literature to investigate the incidence of abnormal imaging findings and various factors in disease relapse. It was found that the incidence of abnormal findings by scintigraphy was significantly higher than that by computed tomography (P = 0.0057). The duration of intravenous antibiotic administration of the relapse group (14.7 +/- 4.7 days) was significantly shorter than that of the non-relapse group (24.3 +/- 10.7 days; P = 0.0376). The statistical analysis suggested that intravenous antibiotic administration is necessary at least for 20 days to prevent a relapse of PS.

This study reports an unusual case of acute leukemia which was diagnosed as hemophilia A on initial admission for leukemia. A 3 year old boy was admitted to Kagoshima University Hospital with anemia. He was diagnosed as acute lymphoblastic leukemia. At the same time he was revealed to have severe hemophilia A- without any previous episodes of severe bleeding tendency or family history of this disease. The laboratory investigation showed his mother to be a carrier of hemophilia A. Although there are many cases of hemophilia which have developed malignant tumors, most of them were caused by association with human immunodeficiency virus (HIV) infection. Only five cases with coexistence of leukemia and hemophilia without HIV infection have been reported and the present case is the first one in Japan. At this stage, hemophiliacs are not necessarily regarded to be a population at risk for the development of leukemia. Furthermore, no particular subtype of leukemia was characterized among these patients in the literature.

A five-year-old boy initially diagnosed common ALL was developed to acute myelomonocytic leukemia. At onset, the bone marrow was hypercellular and 77% of the cells were blasts, mainly lymphoblast-like cells and cytogenetic study demonstrated 45, XY, -7 in all blasts. Cytochemically most of those blasts were negative for peroxidase, sudan black B, alpha-NB esterase staining. The immunological phenotype was J5 (CD10)+, I2 (HLA-DR)+, SmIg-, CyIgmu-, Leu1 (CD5)-, OKT11 (CD2)-, MY7 (CD13)-, suggesting common ALL. Eight months later, the bone marrow cells were occupied with large sized blasts which were almost positive for peroxidase stain and the cells showed coexpression of Mo1 (CD11b)+, MY4 (CD14)+, MY7+, MY9 (CD33)+, MCS2 (CD13)+, I2+, J5-, B4 (CD19)-, Mo2 (CDw14)-, at relapse. He died 2 years and 6 months after his initial diagnosis. An autopsy was performed which revealed generalized infiltration of leukemic cells and aspergillosis of the lung. In general, monosomy 7 is associated with myelodysplastic syndrome in childhood, and is terminated to acute myeloblastic leukemia. In this case, bone marrow blasts demonstrated monosomy 7 cytogenetically, and this case was considered as an acute mixed lineage leukemia of bilineal type. And this case proved that a monosomy 7 can also be terminated to acute mixed lineage leukemia with both lymphoid and myeloid phenotypes.

We report the case of a 14-year-old Japanese boy with peripheral T-cell malignant lymphoma, showing progression from immunoblastic lymphadenopathy (IBL) to overt malignant lymphoma. He suffered recurrent fever, generalized lymphadenopathy, hepatosplenomegaly and maculopapular exanthema. Leukocytosis with eosinophilia and polyclonal hypergammaglobulinemia were observed during the aggressive course of the disease. In the early phase, human immunoglobulin and steroids improved the symptoms but did not induce complete remission, and the patient died one year after the onset of the illness. Four biopsies of lymph nodes revealed progression from IBL to CD4 positive T-cell lymphoma through IBL-like T-cell lymphoma. Though IBL-like T-cell lymphoma is defined as IBL with neoplastic features and overt T-cell malignant lymphoma progressed from IBL-like T-cell lymphoma is excluded from the definition, it may be preferable that such malignant lymphoma as our case should also be included in IBL-like T-cell lymphoma.