Effect of high energy electrons on H⁻ production and destruction in a high current DC negative ion source for cyclotron.

Recently, a filament driven multi-cusp negative ion source has been developed for proton cyclotrons in medical applications. In this study, numerical modeling of the filament arc-discharge source plasma has been done with kinetic modeling of electrons in the ion source plasmas by the multi-cusp arc-discharge code and zero dimensional rate equations for hydrogen molecules and negative ions. In this paper, main focus is placed on the effects of the arc-discharge power on the electron energy distribution function and the resultant H(-) production. The modelling results reasonably explains the dependence of the H(-) extraction current on the arc-discharge power in the experiments.

High current DC negative ion source for cyclotron.

A filament driven multi-cusp negative ion source has been developed for proton cyclotrons in medical applications. In Cs-free operation, continuous H(-) beam of 10 mA and D(-) beam of 3.3 mA were obtained stably at an arc-discharge power of 3 kW and 2.4 kW, respectively. In Cs-seeded operation, H(-) beam current reached 22 mA at a lower arc power of 2.6 kW with less co-extracted electron current. The optimum gas flow rate, which gives the highest H(-) current, was 15 sccm in the Cs-free operation, while it decreased to 4 sccm in the Cs-seeded operation. The relationship between H(-) production and the design/operating parameters has been also investigated by a numerical study with KEIO-MARC code, which gives a reasonable explanation to the experimental results of the H(-) current dependence on the arc power.

Development of a high current H(-) ion source for cyclotrons.

A multi-cusp DC H(-) ion source has been designed and fabricated for medical applications of cyclotrons. Optimization of the ion source is in progress, such as the improvement of the filament configuration, magnetic filter strength, extraction electrode's shape, configuration of electron suppression magnets, and plasma electrode material. A small quantity of Cs has been introduced into the ion source to enhance the negative ion beam current. The ion source produced 16 mA of DC H(-) ion beam with the Cs-seeded operation at a low arc discharge power of 2.8 kW.

Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.

AIMS/HYPOTHESIS: The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. METHODS: Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. RESULTS: BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. CONCLUSIONS/INTERPRETATION: In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.

Portal venous tumor thrombus associated with hepatic metastasis of renal cell carcinoma: case report.

We report a case of liver metastasis of renal cell carcinoma with portal venous tumor thrombus. Abdominal computed tomographic images showed a large hepatic mass that enhanced slightly during arterial phase. Multiple hypoattenuating lesions were seen in the intrahepatic portal venous branches and were traced directly from the mass. The histologic specimen confirmed metastatic liver tumor of renal cell carcinoma with portal venous tumor thrombus.

Antibacterial activity of phytochemicals isolated from Erythrina zeyheri against vancomycin-resistant enterococci and their combinations with vancomycin.

Six phytochemicals were isolated from the roots of Erythrina zeyheri (Leguminosae) by repeated silica gel column chromatography using various eluting solvents. Extensive spectroscopic studies revealed that all were isoflavonoids. The antibacterial activity of the six compounds against vancomycin-resistant enterococci (VRE) was estimated by determining the minimum inhibitory concentration (MIC). Of the six isoflavonoids, erybraedin A ((6aR, 11aR)-3,9-dihydroxy-4,10-di(gamma,gamma-dimethylallyl)pterocarpan) exhibited the highest growth inhibitory potency against VRE with an MIC value of 1.56-3.13 microg/mL, followed by eryzerin C ((3R)-7,2',4'-trihydroxy-6,8-di(gamma,gamma-dimethylallyl)isoflavan) (MIC 6.25 microg/mL). These compounds also inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.13-6.25 microg/mL. The antibacterial effects of the two compounds against VRE and MRSA were based on bacteriostatic action. When erybraedin A or eryzerin C was combined with vancomycin, the fractional inhibitory concentration (FIC) index against VRE ranged from 0.5306 to 1.0 and from 0.5153 to 0.75, respectively. The combinations also showed FIC indices of 0.6125-1.0 against MRSA. The results indicate that, depending on the case, both compounds act either synergistically or additively with vancomycin against VRE and MRSA. Erybraedin A and eryzerin C show evidence of being potent phytotherapeutic agents against infections caused by VRE and MRSA.

Antibacterial properties of a new isoflavonoid from Erythrina poeppigiana against methicillin-resistant Staphylococcus aureus.

A new isoflavonoid, together with four known isoflavonoids, was isolated from the roots of Erythrina poeppigiana. The chemical structure was determined by extensive spectroscopic studies, and then its antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) was investigated. The new isoflavonoid was identified as 3,9-dihyroxy-10-gamma,gamma-dimethylallyl-6a,11a-dehydropterocarpan (compound 1). Compound 1 inhibited bacterial growth most potently of the five isolates, and had a minimum inhibitory concentration (MIC) of 125 microg/ml against thirteen MRSA strains. Inhibitory activity was based on bactericidal action and viable cell number reduced by approximately 1/10,000 after 4 h incubation with compound 1. Despite intense bactericidal action against MRSA, compound 1 never resulted in leakage of 260 nm-absorbing substances from bacterial cells. Compound 1 (12.5 microg/ml) completely inhibited incorporation of radio-labeled thymidine, uridine and leucine into MRSA cells. Although glucose incorporation was also markedly inhibited by the compound, the amount of glucose incorporated by bacterial cells increased gradually with incubation time. These findings suggest that compound 1 exhibits anti-MRSA activity by interfering with incorporation of metabolites and nutrients into bacterial cells or by affecting the nucleic acids of MRSA cells. Furthermore, this new compound could be a potent phytotherapeutic agent for treating MRSA infections.

Antibacterial property of isoflavonoids isolated from Erythrina variegata against cariogenic oral bacteria.

The antibacterial property of 7 compounds, isolated from Erythrina variegata (Leguminosae) by repeated silica gel column chromatography, against cariogenic oral bacteria was investigated. Extensive spectroscopic study revealed that all were isoflavonoids. Among them, 3,9-dihydroxy-2,10-di(gamma,gamma-dimethylallyl)-6a,11a-dehydropterocarpan (erycristagallin) showed the highest antibacterial activity against mutans streptococci, other oral streptococci, Actinomyces and Lactobacillus species with a minimum inhibitory concentration (MIC) range of 1.56-6.25 microg/ml, followed by 3,6a-dihydroxy-9-methoxy-2,10-di(gamma,gamma-dimethylallyl)pterocarpan (erystagallinA) and 9-hydroxy-3-methoxy-2-gamma,gamma-dimethylallylpterocarpan (orientanol B) (MIC range: 3.13-12.5 microg/ml). The antibacterial effect of erycristagallin to mutans streptococci was based on a bactericidal action. Erycristagallin (6.25 microg/ml: MIC) completely inhibited incorporation of radio-labelled thymidine into Streptococcus mutans cells. Incorporation of radio-labelled glucose into bacterial cells was also strongly inhibited at MIC, and 1/2 MIC of the compound reduced the incorporation approximately by half. The findings indicate that erycristagallin has a potential as potent phytochemical agent for prevention of dental caries by inhibiting the growth of cariogenic bacteria and by interfering with incorporation of glucose responsible for production of organic acids.

Erythrina poeppigiana-derived phytochemical exhibiting antimicrobial activity against Candida albicans and methicillin-resistant Staphylococcus aureus.

AIMS: To screen five phytochemicals isolated from Erythrina poeppigiana (Leguminosae) for antimicrobial activity against both Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: Roots of E. poeppigiana were macerated with acetone and the chloroform-soluble fraction of the residue was subjected to repeated silica gel column chromatography using various eluting solvents. Structures of the isolated compounds were determined by extensive spectroscopic studies. Each compound was dissolved in dimethyl sulphoxide and added to agar plates (final concentration: 1.56-100 microg ml(-1)) and minimum inhibitory concentrations (MICs) against C. albicans and MRSA were determined. Spectral data indicated the presence of three different types of phytochemicals; isoflavonoids (erypoegin A, demethylmedicarpin and sandwicensin), alpha-methyldeoxybenzoin (angolensin) and cinnamylphenol (erypostyrene). While all compounds showed anti-MRSA activity in this concentration range, isoflavonoids and alpha-methyldeoxybenzoin failed to inhibit the growth of C. albicans. Erypostyrene (E-1-[2-hydroxy-4-methoxy-5-(gamma,gamma-dimethylallyl)benzyl]-2-(4-hydroxyphenyl)ethylene) exhibited not only the highest anti-MRSA activity (MIC value of 6.25 microg ml(-1)) but also anti-candidal potency (MIC value of 50 microg ml(-1)). The compound reduced viable cell numbers of C. albicans and MRSA by approximately 1 of 2000 and 1 of 1000 after 1 h incubation at each MIC, respectively. CONCLUSIONS: A new cinnamylphenol, erypostyrene, possessed anti-candidal and anti-MRSA activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Erypostyrene could be a leading candidate for development of antimicrobial agents with anti-candidal and anti-MRSA activity.

Antibacterial activity of isoflavonoids isolated from Erythrina variegata against methicillin-resistant Staphylococcus aureus.

AIMS: To screen 16 isoflavonoids isolated from Erythrina variegata (Leguminosae) for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: The roots of E. variegata were macerated with acetone. The chloroform-soluble fraction of the residue was subjected to repeated silica gel column chromatography followed by elution with various solvents. Structures of the isolated compounds were determined by extensive spectroscopic studies. Each compound was dissolved in dimethyl sulphoxide and added to agar plates (final concentration 1.56-100 microg ml(-1) and suspensions of MRSA spotted onto the agar plates to determine the minimum inhibitory concentration (MIC). Repeated silica gel chromatography yielded 16 compounds and spectroscopic studies revealed that all were isoflavonoids. Whilst 14 compounds showed antibacterial activity in this concentration range, the MIC values varied significantly among them. Of the active compounds, 3,9-dihydroxy-2,10-di(gamma,gamma-dimethylallyl)-6a,11a-dehydropterocarpan (erycristagallin) and 9-hydroxy-3-methoxy-2-gamma,gamma-dimethylallylpterocarpan (orientanol B) exhibited the highest activity with MIC values of 3.13-6.25 microg ml(-1). CONCLUSIONS: Erycristagallin and orientanol B showed the highest anti-MRSA activity (3.13-6.25 microg ml(-1). SIGNIFICANCE AND IMPACT OF THE STUDY: Erycristagallin and orientanol B could be leading compounds for phytotherapeutic agents against MRSA infections.

Erythrinan alkaloids and isoflavonoids from Erythrina poeppigiana.

A new erythrinan alkaloid, 8-oxo-alpha-erythroidine epoxide, was isolated from wood of Erythrina poeppigiana together with the five known compounds, 8-oxo-alpha-erythroidine, erystagallin C, alpinumisoflavone, erythrinin C and eryvarin A. Their structures were elucidated on the basis of spectroscopic evidence.

Revised structures for senegalensin and euchrenone b(10).

Two prenylated isoflavones (1 and 2) with a hydroxyisopropyldihydrofuran moiety have been isolated from the wood of Erythrina suberosa var. glabrescence. The structure of compound 1 was in agreement with that of the previously reported senegalensin, isolated from the stem bark of Erythrina senegalensis. The structure of senegalensin was revised from structure 2 to structure 1 by spectroscopic means. Compound 2, the regioisomer of 1, was confirmed as euchrenone b(10) by comparison with the spectral data of the reported euchrenone b(10), isolated from the roots of Euchresta horsfieldii. The structure of 2 was established by 2D NMR spectroscopic analysis and by the X-ray crystallographic analysis of its p-bromobenzoyl derivative (2b).

Erysubins C-F, four isoflavonoids from Erythrina suberosa var. glabrescences.

Four isoflavonoids, erysubins C-F, together with ten known compounds were isolated from the roots of Erythrina suberosa var. glabrescences, and their structures were elucidated on the basis of spectroscopic evidence. Erysubin C is an unusual pterocarpan derivative with a formyl group.

Cis-N-(p-Coumaroyl)serotonin from Konnyaku, Amorphophallus konjac K. Koch.

Tobiko is produced as a by-product in the manufacture of konnyaku and comes to about 45% of dried konnyaku-imo. For a possible use of this powder, we studied its components. Serotonin, trans-N-(p-coumaroyl) serotonin, and a new compound, cis-N-(p-coumaroyl)serotonin, were characterized from this powder.

Expression of the SART3 tumor rejection antigen in renal cell carcinoma.

PURPOSE: We recently reported that SART3 tumor rejection antigen is recognized by HLA class I restricted cytotoxic T lymphocytes from patients with esophageal cancer. We now investigate the expression of SART3 antigen in renal cell carcinoma to identify an appropriate molecule that may be used in specific immunotherapy of renal cell carcinoma. MATERIALS AND METHODS: Renal cell carcinoma and nontumorous kidney tissues were obtained at surgery. A section of each sample was minced with scissors and stored at -80C until use. SART3 antigen expression was examined in uncultured renal cell carcinoma and nontumorous kidney tissues. We also evaluated the ability of derived peptides to include cytotoxic T lymphocytes in peripheral blood mononuclear cells from patients with renal cell carcinoma. RESULTS: The SART3 antigen was detected in all renal cell carcinoma cell lines, primary cultures of renal cell carcinoma and nontumorous kidney tissues, and in the cytosol of 57% and 15% of renal cell carcinoma and nontumorous kidney tissues, respectively. HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes (KE4) used in cloning of the SART3 gene were significantly cytotoxic to cells from renal cell carcinoma cell lines and primary cultures of renal cell carcinoma tissue but they did not lyse normal cells, including those from primary cultures of nontumorous kidney tissue. The SART3 peptides derived from positions 109-118 and 315-323 induced HLA-A24 restricted cytotoxic T lymphocytes to renal cell carcinoma cells from peripheral blood mononuclear cells of patients with renal cell carcinoma. CONCLUSIONS: The SART3 antigen and derived peptides may be applied to the specific immunotherapy of HLA-A24+ renal cell carcinoma.

Two new isoflavonoids from Erythrina variegata.

Two new isoflavonoids, eryvarin A (1) and eryvarin B (2) were isolated from the wood of Erythrina variegata and their structures were elucidated on the basis of spectroscopic evidence.

Carotenoids in human blood plasma after ingesting paprika juice.

We investigated the presence of different carotenoids in male human subject after the ingestion of paprika juice, and identified capsanthin, capsanthone, cucurbitaxanthin A, 11-cis-capsanthin, lutein and zeaxanthin in the human plasma. These results suggest that capsanthone and 11-cis-capsanthin might be as important as capsanthin for human health.

Analysis of initial fouling process in coastal environment: effects of settlement, attachment, and metamorphosis promoters.

Effects of lumichrome, L-tryptophan, and curcumin on fouling organisms were examined on panels immersed in a near-shore aquatic environment. These products showed effective action in aquariums in preliminary screening tests for promoting different steps of fouling. Lumichrome showed metamorphosis-inducing activity for ascidian larvae (Halocynthia), L-tryptophan was a settlement-inducer for larvae of barnacles (Balanus), and curcumin showed attachment-promoting activity on the blue mussel (Mytilus). In order to establish that these tests are helpful in screening actual fouling or antifouling compounds, we examined the action of these three compounds in a coastal environment by following the first steps of biofouling, that is, by studying the quantity of chlorophyll, the number of bacterial cells, and the larvae settled. These experiments on the seashore indicated that these compounds did not act as promoters for the target organisms; however, they did show promoting effects on some nontarget organisms.

[The relationship between the tumor uptake of gallium-67 and the effect of cisplatin-based preoperative chemotherapy or chemoradiotherapy for lung cancer].

Cisplatin has been usually used as the chemotherapy for lung cancer presurgically, though it is still difficult to predict downstaging of tumor from this drug. Four patients who underwent surgery achieved pathologic complete remissions in response to preoperative cisplatin-based chemotherapy with or without radiation. All of the Ga-67 citrate images in the four patients showed markedly increased uptake in tumors. According to the literatures, both Ga-67 and cisplatin binds to transferrin in the blood and transfers into the cells through transferrin-receptors expressed on the cell surface. The mechanism for Ga-67 and cisplatin uptake into tumor cells were alike. Marked tumor uptake on Ga-67 scintigraphy suggested that cisplatin-based chemotherapy or chemoradiotherapy was efficacious.

Cancer chemopreventive activity of euglobal-G1 from leaves of Eucalyptus grandis.

In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Eucalyptus plants were screened. Consequently, the phlorogrucinol-monoterpene derivative, euglobal-G1 (EG-1), was obtained from the leaves of Eucalyptus grandis as an active constituent. EG-1 exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA) as an initiator and fumonisin-B1, which has been known as one of mycotoxins produced by Fusarium monifliforme, as a promoter. Further, EG-1 exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary tumor using 4-nitroquinoline-N-oxide (4-NQO) as an initiator and glycerol as a promoter.