Introduction to The neurosciences and music IV: learning and memory.

The conference entitled "The Neurosciences and Music-IV: Learning and Memory'' was held at the University of Edinburgh from June 9-12, 2011, jointly hosted by the Mariani Foundation and the Institute for Music in Human and Social Development, and involving nearly 500 international delegates. Two opening workshops, three large and vibrant poster sessions, and nine invited symposia introduced a diverse range of recent research findings and discussed current research directions. Here, the proceedings are introduced by the workshop and symposia leaders on topics including working with children, rhythm perception, language processing, cultural learning, memory, musical imagery, neural plasticity, stroke rehabilitation, autism, and amusia. The rich diversity of the interdisciplinary research presented suggests that the future of music neuroscience looks both exciting and promising, and that important implications for music rehabilitation and therapy are being discovered.

Evaluation of image quality in portal imaging using a combination of a storage phosphor plate and diagnostic cassette.

It is useful to utilise a computed radiography system with a combination of storage phosphor plates and therapy cassettes for portal images. However, the therapy cassette has some disadvantages. The objective of the present study was to determine whether the disadvantages of a diagnostic cassette could be overcome to obtain clinically useful portal images. A storage phosphor plate has 0.3 mm of lead foil on the distal surface to reduce backscattered radiation. When the plate is reversed, the lead foil acts as a front intensifying screen, similar to the metal plate of a therapy cassette. We reversed a combination of the diagnostic cassette and storage phosphor plate and obtained portal images of the contrast-detail phantom and the Rando phantom (The Phantom Laboratory, Salem, NY) using three types of cassettes: a reversed diagnostic cassette, a therapy cassette and a diagnostic cassette. The image quality was subjectively evaluated. The Friedman and Wilcoxon tests were applied for statistical analyses. Evaluation of images for the contrast-detail phantom revealed that the reversed diagnostic cassette was inferior to the therapy cassette and superior to the diagnostic cassette, and that the differences were significant (p<0.017). There was no significant difference between the reversed diagnostic cassette and therapy cassette (p>0.05) for the Rando phantom. Portal images obtained using the reversed diagnostic cassette were of sufficiently high quality for clinical use as determined by Rando phantom studies.

A new diglycosyl megastigmane from Carallia brachiata.

A new megastigmane diglycoside was isolated from the leaves of Carallia brachiata. The structure was determined by spectroscopic methods as 3-hydroxy-5,6-epoxy-beta-ionol -3-O-beta-apiofuranosyl-(1-->6)-beta-glucopyranoside (1). Additionally, 29 known compounds consisting of two megastigmanes, one 1,2-dithiolane derivative, seven aromatic compounds, five condensed tannins, 12 flavonoids, and two glyceroglycolipids were isolated and identified.

Cortical oscillations modulated by congruent and incongruent audiovisual stimuli.

Congruent or incongruent grapheme-phoneme stimuli are easily perceived as one or two linguistic objects. The main objective of this study was to investigate the changes in cortical oscillations that reflect the processing of congruent and incongruent audiovisual stimuli. Graphemes were Japanese Hiragana characters for four different vowels (/a/, /o/, /u/, and /i/). They were presented simultaneously with their corresponding phonemes (congruent) or non-corresponding phonemes (incongruent) to native-speaking Japanese participants. Participants' reaction times to the congruent audiovisual stimuli were significantly faster by 57 ms as compared to reaction times to incongruent stimuli. We recorded the brain responses for each condition using a whole-head magnetoencephalograph (MEG). A novel approach to analysing MEG data, called synthetic aperture magnetometry (SAM), was used to identify event-related changes in cortical oscillations involved in audiovisual processing. The SAM contrast between congruent and incongruent responses revealed greater event-related desynchonization (8-16 Hz) bilaterally in the occipital lobes and greater event-related synchronization (4-8 Hz) in the left transverse temporal gyrus. Results from this study further support the concept of interactions between the auditory and visual sensory cortices in multi-sensory processing of audiovisual objects.

The auditory evoked magnetic fields to very high frequency tones.

We studied the auditory evoked magnetic fields (AEFs) in response to pure tones especially at very high frequencies (from 4000 Hz to 40,000 Hz). This is the first systematic study of AEFs using tones above 5000 Hz, the upper audible range of humans, and ultrasound. We performed two experiments. In the first, AEFs were recorded in 12 subjects from both hemispheres under binaural listening conditions. Six types of auditory stimulus (pure tones of five different frequencies: 4000 Hz, 8000 Hz, 10,000 Hz, 12,000 Hz, 14,000 Hz, and a click sound as the target stimulus) were used. In the second experiment, we used 1000 Hz, 15,000 Hz, and two ultrasounds with frequencies of 20,000 Hz and 40,000 Hz. The subjects could detect all stimuli in the first experiment but not the ultrasounds in the second experiment. We analyzed N1m, the main response with approximately 100 ms in peak latency, and made the following findings. (1) N1m responses to the tones up to 12,000 Hz were clearly recorded from at least one hemisphere in all 12 subjects. N1m for 14,000 Hz was identified in at least one hemisphere in 10 subjects, and in both hemispheres in six subjects. No significant response could be identified to ultrasounds over 20,000 Hz. (2) The amplitude of the N1m to the tones above 8000 Hz was significantly smaller than that to 4000 Hz in both hemispheres. There was a tendency for the peak latency of the N1m to be longer for the tones with higher frequencies, but no significant change was found. (3) The equivalent current dipole (ECD) of the N1m was located in the auditory cortex. There was a tendency for the ECD for the tones with higher frequencies to lie in more medial and posterior areas, but no significant change was found. (4) As for the interhemispheric difference, the N1m amplitude for all frequency tones was significantly larger and the ECDs were estimated to be located more anterior and medial in the right hemisphere than the left. The priority of the right hemisphere, that is the larger amplitude, for very high frequency tones was confirmed. (5) The orientation of the ECD in the left hemisphere became significantly more vertical the higher the tones. This result was consistent with previous studies which revealed the sensitivity of the frequency difference in the left hemisphere. From these findings we suggest that tonotopy in the auditory cortex exists up to the upper limit of audible range within the small area, where the directly air-conducted ultrasounds are not reflected.

Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy.

This study investigated the relationship between the drug combinations of the eradication regimens and the prevalence of acquired resistance to clarithromycin. Of 540 patients treated with anti-Helicobacter pylori regimens containing clarithromycin, 55 patients (31 males, mean age, 45.6 years) with failed eradication of H. pylori that was susceptible to clarithromycin before treatment were included. The E test was used to test for susceptibility to clarithromycin (minimum inhibitory concentration (MIC) <1 mg/l). Of the 55 patients, 33 (60.0%) developed clarithromycin resistance after failed eradication. Of the dual therapies, the combination of a proton pump inhibitor (PPI) and clarithromycin resulted in 88.9% (8/9) of the patients acquiring clarithromycic-resistance. With the triple therapies, the percentages of patients acquiring clarithromycin resistant strains after using a PPI+clarithromycin+amoxycillin or a PPI+clarithromycin+metronidazole were 38.7% (12/31) and 90.0% (9/10), respectively (P<0.01). These data suggest that regimens containing amoxycillin may prevent the selection of secondary clarithromycin resistance.

[Lymphedema after radical prostatectomy: a case report].

We report a case of intractable lymphedema of the left leg following radical prostatectomy. The 69-year-old male patient complained of difficulty walking, caused by severe lymphedema. Intraarterial autologous lymphocyte transfusion therapy was performed because of failure of conventional conservative therapy, and the leg edema resolved almost completely. However, the treatment did not improve the penoscrotal edema necessitating excision of the edema and skin graft in a separate procedure. The post-operative course was excellent and the patient's performance status improved to 1 from 3.

A multicenter, double-blind study on triple therapy with lansoprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers. METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d. (Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d. (Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment. RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2% (95% CI: 84.8-93.7%) and 86.4% (95%CI: 81.5-91.3%) in total in the full analysis set, 89% (95% CI: 84.3-93.7%) and 85.3% (95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both). CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

Further evidence for the involvement of insulin receptor substrates in epidermal growth factor-induced activation of phosphatidylinositol 3-kinase.

In accordance with our recent results obtained with cultured rat hepatocytes [Fujioka, T. & Ui, M. (2001) Eur. J. Biochem. 268, 25-34], epidermal growth factor (EGF) gave rise to transient tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), thereby activating the bound phosphatidylinositol 3-kinase in human epidermoid carcinoma A431 cells normally abundant in EGF receptors (EGFR) and Chinese hamster ovary (CHO) cells transfected with full-length EGFR. These actions of EGF, although much smaller in magnitude than those of insulin or IGF-I in the same cells, were accompanied by tyrosine phosphorylation of EGFR rather than insulin or IGF-I receptors, never observed in wild-type CHO cells expressing no EGFR, and totally inhibited by an inhibitor of EGFR kinase, AG1478, that was without effect on insulin or IGF-I actions. Recombinant IRS-1 was phosphorylated on tyrosines upon incubation with purified EGFR from A431 cells and 32P-labeled ATP. When CHO cells were transfected with C-terminal truncated EGFR lacking three NPXY motifs responsible for direct binding to phosphotyrosine-binding domains of IRSs, no effect of EGF could be observed. We suggest that tyrosine phosphorylation of IRS-1 or IRS-2 could mediate EGFR-induced activation of phosphatidylinositol 3-kinase in mammalian cells.

Biodisposition of FITC-labeled aloemannan in mice.

Biodisposition of FITC-labeled aloemannan (F-AM) with the homogenate from some organs in mice was demonstrated. F-AM was metabolized only by the mucosa from the large intestine into smaller molecules that were effectively absorbed in mice. The homogenate from the other tissues did not affect the metabolism of F-AM. The degraded product (1) of F-AM after incubation with 10% feces homogenate for 24 h was chromatographed on a highly porous polymer and a Sephadex LH-20 column to provide an FITC-degraded fraction (2), which was shown to have a molecular weight of 800 D on Sephadex G-25 gel permeation. Metabolite 2 was examined by physicochemical methods and shown to be a mixture of FITC-hexose and -2 hexose on FAB-MS. An FITC-degraded fraction (3) with a molecular weight of 3 KD was obtained by 6-h incubation with 10% feces homogenate on Sephadex G-25 column chromatography and was shown to be a mixture of FITC-9 and 12 x hexose on TOF-MS.

Development of anti-influenza drugs: II. Improvement of oral and intranasal absorption and the anti-influenza activity of stachyflin derivatives.

The in-vivo anti-influenza-virus activity of Stachyflin derivatives (III and its phosphate ester, III-Phos), a new class of haemagglutinin fusion inhibitor, and the improvement of their absorption after oral or intranasal administration were studied in mice, rats, and ferrets. The absorption of III in PEG 4000 and III-Phos aqueous solution increased about three and four fold in AUC after oral administration to uninfected mice compared with that of 0.5% HPMC (hydroxypropyl-methylcellulose) suspension. Using a mouse influenza virus infection model, significant anti-influenza-virus activity was observed in infected mice treated orally with these compounds dissolved in PEG 4000 or distilled water, respectively, but not in mice treated with 0.5% HPMC. The in-vivo anti-influenza-virus activity in ferrets, a good model for influenza virus infection in man, was also studied. Although the concentration of III in plasma was above the IC50 against the influenza virus strain used for 6h after the oral administration of III in PEG 400 to uninfected ferrets, no in-vivo anti-influenza-virus activity was observed at the same dosage given 4 times daily for 3 days. The intranasal administration of III-Phos, which was expected to have a more notable in-vivo anti-influenza-virus activity, was examined. III-Phos, whose intranasal absorption had been improved by the modification of III with phosphate ester in rats, inhibited viral replication in the nasal cavity and suppressed influenza-virus-induced fever when administered intranasally to infected ferrets. This study demonstrates that intranasally administered compounds with anti-influenza-virus activity must permeate the nasal membranes to produce their anti-influenza-virus effect.

Effect of Saireitoh on rabbit smooth muscle cell proliferation and experimental atherosclerosis.

Saireitoh is a traditional Chinese medicine that is often given to patients with nephrotic syndrome or glomerulonephritis. Studies have reported that Saireitoh stimulates intrinsic steroid secretion in rats and suppresses the proliferation of fibroblasts in vitro. We examined the effects of Saireitoh on vascular smooth muscle cell proliferation and migration in vitro and experimental atherosclerosis in vivo. Saireitoh rabbit serum obtained from New Zealand White rabbits which were given a diet containing 2% Saireitoh for 3 days significantly inhibited [3H]-thymidine incorporation by smooth muscle cells, which were isolated from thoracic aorta explants of rabbits. The addition of 10% Saireitoh rabbit serum to a culture medium containing smooth muscle cells inhibited DNA synthesis by 50% as compared with a control culture to which 10% normal rabbit serum was added. We also found that the number of smooth muscle cells in the culture containing Saireitoh rabbit serum was decreased. When PDGF was used as a chemoattractant, we demonstrated that Saireitoh rabbit serum slightly inhibits the migration of smooth muscle cells. In in vivo experiments, Saireitoh did not suppress the development of atherosclerosis but tended to reduce the damage. We concluded that although Saireitoh inhibited the proliferation of smooth muscle cells, the effect of prevention on the development of atherosclerosis is weak in the in vivo condition.

Decreases in cAMP phosphodiesterase activity in hepatocytes cultured with herbimycin A due to cellular microtubule polymerization related to inhibition of tyrosine phosphorylation of alpha-tubulin.

The increase in cellular cAMP concentration during 10-min incubation of rat hepatocytes with glucagon or forskolin was enhanced markedly when the hepatocytes had been cultured for several hours with herbimycin A. This effect of herbimycin was accompanied by inhibition of tyrosine-phosphorylation of cellular proteins including alpha-tubulin, antagonized by coaddition of Na3VO4 plus H2O2, which also antagonized the herbimycin-induced tyrosine phosphorylation, and overcome by the addition to the 10-min incubation medium of a certain inhibitor of cAMP phosphodiesterase (PDE), which caused a huge accumulation of cAMP. The effective PDE inhibitors were 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone (rolipram) and 4-(3-butyloxy-4-methoxyphenyl)-2-imidazolidinone (Ro-20-1724, a PDE4 inhibitor), in addition to 3-isobutyl-1-methylxanthine (a nonselective inhibitor). Rapid breakdown of the once-accumulated cAMP in cultured hepatocytes during the subsequent incubation without PDE inhibitors was progressively prevented when the concentration of herbimycin was increased from 0.3 to 10 microM during prior culture. This effect of herbimycin to inhibit PDE activity in intact cells was abolished by coaddition of a microtubule-disrupting agent, either colchicine or vinblastine, into the culture, but remained unchanged if the vinblastine-containing medium was further supplemented with taxol, a microtubule-stabilizing agent, which by itself mimicked the effect of herbimycin. None of these agents, which thus affected PDE activity in intact cells, inhibited the PDE activity assayable in the cell lysates. The taxol-like and vinblastine-suppressible action of herbimycin to stimulate microtubular assembly was antagonized by Na3VO4/H2O2, as confirmed by confocal microscopic images of the cells stained with fluorescein-bound anti-(alpha-tubulin). Thus, 4-h culture of hepatocytes with herbimycin inhibits phosphorylation of the C-terminal tyrosine residue of alpha-tubulin, thereby stimulating formation of a microtubular network which is responsible for the inhibition of PDE4 in the intact cells by an unknown mechanism.

Antiproliferative constituents from umbelliferae plants. V. A new furanocoumarin and falcarindiol furanocoumarin ethers from the root of Angelica japonica.

The CHCl3 extract of the root of Angelica japonica showed high inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth. From this extract, a new furanocoumarin named japoangelone and four furanocoumarin ethers of falcarindiol, named japoangelols A-D, were isolated together with caffeic acid methyl ester, four polyacetylenic compounds (panaxynol, falcarindiol, 8-O-acetylfalcarindiol, and (9Z)-1,9-heptadecadiene-4,6-diyne-3,8,11-triol), eight coumarins (osthol, isoimperatorin, scopoletin, byakangelicin, xanthotoxin, bergapten, oxypeucedanin methanolate, and oxypeucedanin hydrate), and two chromones (3'-O-acetylhamaudol, and hamaudol). The structures of the new isolates were determined based on spectral evidence. The ED50 of isolates against MK-1, HeLa, and B16F10 cell lines are reported.

Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids.

Oleanolic acid (1) was identified as an anti-HIV principle from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phoradendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). It inhibited HIV-1 replication in acutely infected H9 cells with an EC50 value of 1.7 microg/mL, and inhibited H9 cell growth with an IC50 value of 21.8 microg/mL [therapeutic index (T. I.) 12.8]. Pomolic acid, isolated from R. woodsii and H. capitata, was also identified as an anti-HIV agent (EC50 1.4 microg/mL, T. I. 16.6). Although ursolic acid did show anti-HIV activity (EC50 2.0 microg/mL), it was slightly toxic (IC50 6.5 microg/mL, T. I. 3.3). A new triterpene (11) was also isolated from the CHCl3-soluble fraction of R. woodsii, though it showed no anti-HIV activity. The structure of 11 was determined to be 1beta-hydroxy-2-oxopomolic acid by spectral examination. Based on these results, we examined the anti-HIV activity of oleanolic acid- or pomolic acid-related triterpenes isolated from several plants. In addition, we previously demonstrated that derivatives of betulinic acid, isolated from the leaves of S. claviflorum as an anti-HIV principle, exhibited extremely potent anti-HIV activity. Accordingly, we prepared derivatives of oleanolic acid and evaluated their anti-HIV activity. Among the oleanolic acid derivatives, 18 demonstrated most potent anti-HIV activity, with an EC50 value of 0. 0005 microg/mL and a T. I. value of 22 400.

Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines.

Nine new triterpene glucosides, named cumingianosides G-O (4-7, 9, 12-15), containing a 14,18-cycloapotirucallane-type skeleton were isolated from a cytotoxic fraction of the leaves of Dysoxylum cumingianum. The structures of the new compounds were established on the basis of chemical and spectral examinations. Evaluation of the cytotoxic activity of cumingianosides G-O showed that cumingianoside M exhibited significant (< 4 microM) cytotoxicity, especially against leukemia and melanoma cell lines.

Antitumor agents. 169 Dysoxylum cumingianum. V. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum.

Detailed chemical studies on the cytotoxic fraction from the leaves of Dysoxylum cumingianum have resulted in the isolation of two new triterpene glucosides, cumingianosides P (18) and Q (19), with an apotirucallane-type skeleton. The structures of 18 and 19 were determined by spectral examinations, and by conversion of cumingianosides C (3) and A (1) into 18 and 19, respectively. The cytotoxicities of cumingianosides P and Q against over 50 human cancer cell lines were evaluated. Cumingianoside P exhibited significant (EC50 < 4 microM) cytotoxicity against 37 human cancer cell lines. Among them, the UO-31 (renal cancer) cell line was the most sensitive to this compound (EC50 0.267 microM). In contrast, cumingianoside Q showed selective cytotoxicity against NCI-H522 (non-small cell lung cancer) cells with an EC50 value of 1.67 microM, and exhibited no cytotoxicity (EC50 > 10 microM) against most of the remaining cancer cell lines.

Sofalcone for treatment of Helicobacter pylori infection.

It is difficult to regard sofalcone as a single drug for the treatment of Helicobacter pylori infection. However, sofalcone exerts multiple effects against H. pylori: it has antibacterial activity, induces morphological changes, inhibits adhesion to gastric mucin and inhibits lipolytic activity. The safety profile of sofalcone even on long-term administration is well established. Therefore, it may be possible to establish a new triple therapy for H. pylori infection using sofalcone combined with antibacterial drugs and proton pump inhibitors.

Anti-AIDS agents--XIX. Neotripterifordin, a novel anti-HIV principle from Tripterygium wilfordii: isolation and structural elucidation.

A new kaurane type diterpene lactone, neotripterifordin (1), has been isolated from the roots of Tripterygium wilfordii. The structure of 1 was elucidated by spectroscopic methods, which included the concerted application of a number of 2-D NMR techniques including 1H-1H COSY, phase-sensitive NOESY, HETCOR, and long-range HETCOR. Compound 1 showed potent anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 25 nM and TI of 125.

Hypersensitivity to Japanese cedar (Cryptomeria japonica) pollen in dogs.

Four of 51 dogs with chronic dermatitis were made to react to crude Japanese cedar (Cryptomeria japonica, CJ) pollen allergen by the intradermal skin test (IDST). These four dogs had specific IgE to CJ as determined by Prausnitz-Küstner test. In the provocation test, nasal discharge increased 5 to 20 min after introduction of the crude CJ pollen allergen into the nasal cavities, in two of three dogs. These results demonstrated that these dogs had hypersensitive to CJ pollen, which might be a cause of atopic disease in dogs.