Metabolonote: a wiki-based database for managing hierarchical metadata of metabolome analyses.

Metabolomics - technology for comprehensive detection of small molecules in an organism - lags behind the other "omics" in terms of publication and dissemination of experimental data. Among the reasons for this are difficulty precisely recording information about complicated analytical experiments (metadata), existence of various databases with their own metadata descriptions, and low reusability of the published data, resulting in submitters (the researchers who generate the data) being insufficiently motivated. To tackle these issues, we developed Metabolonote, a Semantic MediaWiki-based database designed specifically for managing metabolomic metadata. We also defined a metadata and data description format, called "Togo Metabolome Data" (TogoMD), with an ID system that is required for unique access to each level of the tree-structured metadata such as study purpose, sample, analytical method, and data analysis. Separation of the management of metadata from that of data and permission to attach related information to the metadata provide advantages for submitters, readers, and database developers. The metadata are enriched with information such as links to comparable data, thereby functioning as a hub of related data resources. They also enhance not only readers' understanding and use of data but also submitters' motivation to publish the data. The metadata are computationally shared among other systems via APIs, which facilitate the construction of novel databases by database developers. A permission system that allows publication of immature metadata and feedback from readers also helps submitters to improve their metadata. Hence, this aspect of Metabolonote, as a metadata preparation tool, is complementary to high-quality and persistent data repositories such as MetaboLights. A total of 808 metadata for analyzed data obtained from 35 biological species are published currently. Metabolonote and related tools are available free of cost at http://metabolonote.kazusa.or.jp/.

Mass++: A Visualization and Analysis Tool for Mass Spectrometry.

We have developed Mass++, a plug-in style visualization and analysis tool for mass spectrometry. Its plug-in style enables users to customize it and to develop original functions. Mass++ has several kinds of plug-ins, including rich viewers and analysis methods for proteomics and metabolomics. Plug-ins for supporting vendors' raw data are currently available; hence, Mass++ can read several data formats. Mass++ is both a desktop tool and a software development platform. Original functions can be developed without editing the Mass++ source code. Here, we present this tool's capability to rapidly analyze MS data and develop functions by providing examples of label-free quantitation and implementing plug-ins or scripts. Mass++ is freely available at http://www.first-ms3d.jp/english/ .

Experimental evaluation of portal venous pulsatile flow synchronized with heartbeat intervals: effects of vascular clamping on portal hemodynamics.

PURPOSE: We previously showed that blood flow in the portal vein was pulsatile and influenced by both the inferior vena cava and the arterial system in a complex manner (Nihei et al., 38:141-149, 2011). The objective of the present study is to identify determinants of blood flow and to clarify the source of pulsatile flow in the portal vein. METHODS: Three-breed terminal crossbreed mini-pigs underwent general anesthesia. Pressure and flow in the portal vein, inferior vena cava, hepatic artery, and mesenteric artery were measured simultaneously. Vascular occluders were placed in the inferior vena cava, hepatic artery, and mesenteric artery to examine the effects of clamping on portal venous flow. RESULTS: Clamping of the mesenteric artery altered pressure and flow waves in the portal vein to waveforms similar to those in the inferior vena cava. Waves resembling those of the inferior vena cava superimposed on portal venous flow appeared later than waves of the inferior vena cava. Clamping of the inferior vena cava promptly altered portal venous pressure and flow. Because clamping of the inferior vena cava led to a sharp rise in portal venous pressure, detailed evaluations were not feasible. Clamping of the hepatic artery had no effect on flow-wave pulsation in the portal vein. CONCLUSIONS: In the hepatic circulation, flow-wave pulsation in the portal vein is influenced by flow in the inferior vena cava via the sinusoids and by flow in the mesenteric artery via the capillary vessels of the intestine.

Experimental evaluation of portal venous pulsatile flow synchronized with heartbeat intervals.

PURPOSE: The aim of this study was to analyze pulsatile flow in the portal vein, to clarify the origin of pulsatile flow, and to acquire new knowledge about the hepatic circulation. METHODS: Mini-pigs underwent general anesthesia. Pressure and flow in the portal vein, inferior vena cava, hepatic artery, and mesenteric artery were measured simultaneously. We (1) studied the relationship between changes in pressure and changes in flow and (2) measured heartbeat intervals and the onset times of pressure and flow waves. RESULTS: In the inferior vena cava, pressure and flow showed mirror-image changes. In the hepatic artery and the mesenteric artery, pressure and flow increased simultaneously. In the inferior vena cava, the longer the heartbeat interval, the more delayed were the onset times of pressure and flow waves. The onset time of pressure and flow waves in the hepatic artery and the mesenteric artery was only minimally affected by changes in heartbeat interval. The relationship between pressure and flow in the portal vein was closer to that in the hepatic artery and the mesenteric artery. However, the onset times of pressure and flow waves in the portal vein showed two different patterns: some showed a pattern similar to that of the inferior vena cava, whereas others showed a pattern similar to that of the hepatic artery and the mesenteric artery. CONCLUSIONS: Blood flow in the portal vein is pulsatile and influenced by both the inferior vena cava and the arterial system in a complex manner.

MassBank: a public repository for sharing mass spectral data for life sciences.

MassBank is the first public repository of mass spectra of small chemical compounds for life sciences (<3000 Da). The database contains 605 electron-ionization mass spectrometry (EI-MS), 137 fast atom bombardment MS and 9276 electrospray ionization (ESI)-MS(n) data of 2337 authentic compounds of metabolites, 11 545 EI-MS and 834 other-MS data of 10,286 volatile natural and synthetic compounds, and 3045 ESI-MS(2) data of 679 synthetic drugs contributed by 16 research groups (January 2010). ESI-MS(2) data were analyzed under nonstandardized, independent experimental conditions. MassBank is a distributed database. Each research group provides data from its own MassBank data servers distributed on the Internet. MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions. In a spectral search to retrieve mass spectra similar to a query mass spectrum, the similarity score is calculated by a weighted cosine correlation in which weighting exponents on peak intensity and the mass-to-charge ratio are optimized to the ESI-MS(2) data. MassBank also provides a merged spectrum for each compound prepared by merging the analyzed ESI-MS(2) data on an identical compound under different collision-induced dissociation conditions. Data merging has significantly improved the precision of the identification of a chemical compound by 21-23% at a similarity score of 0.6. Thus, MassBank is useful for the identification of chemical compounds and the publication of experimental data.

[A case of acinar cell carcinoma of pancreas with liver metastases treated effectively by S-1].

A 65-year-old man underwent a total gastrectomy and distal pancreatectomy for acinar cell carcinoma of the pancreas. Multiple metastatic liver lesions were found one year postoperatively. He was treated with S-1 chemotherapy over 34 months, and the tumors significantly reduced in size without severe side effects. Four years after surgery, the liver metastases increased in size, associated with pain especially in the right upper quadrant. We then performed right hepatectomy. Peritoneal dissemination and multiple lung metastases were found 8 months after liver resection. Acinar cell carcinoma of the pancreas is a rare and highly malignant tumor, and there are few reports regarding treatment with chemotherapy. Herein, we report a case with multiple liver metastases which were controlled by systemic chemotherapy using S-1.

New method of sentinel node detection using a combination of contrast-enhanced ultrasound and dye guidance: an animal study.

PURPOSE: To determine whether a combination of contrast-enhanced ultrasound-guided methods and dye-guided methods can identify sentinel lymph nodes in animals. METHODS: Seven pigs were put under general anesthesia and injected subcutaneously in the neck: three with 2 ml saline and four with 2 ml fluid comprising 0.4 ml 5% patent blue violet solution and 1.6 ml of hydroxyethylated starch (Salinhes) solution (PB + HS). The regional lymph nodes were observed by ultrasound; blue-stained regional lymph nodes found after the skin was cut were situated as ultrasound had shown they would be. RESULTS: The regional lymph nodes of the pigs given saline were unchanged, but in the pigs receiving PB + HS, the echo level in the lymph nodes nearest the injection site was altered, producing a clear contrast with the surrounding tissues. The area of the relevant regional lymph node in each PB + HS-injected pig increased significantly (t-test, P < 0.01; from 25.7, 39.6, 9.36, 70.2 mm(2), and mean, 36.2 mm(2); to 50.7, 65.5, 21.1, 98.3 mm(2), and mean, 58.9 mm(2), respectively). These enlarged regional lymph nodes were easily found by contrast-enhanced ultrasonography. When excised under ultrasound guidance, all were stained blue, indicating that they were sentinel lymph nodes. CONCLUSION: These results suggest that this combination of contrast-enhanced ultrasound-guided and dye-guided methods warrants use as a quick, simple procedure for detecting sentinel lymph nodes.

[Angina attack caused by 5-fluorouracil infusion--report of a case and review of the literature].

Cardiac toxicity of 5-fluorouracil (5-FU) has been rarely reported. We encountered a case of angina attack caused by 5-FU. A 58-year-old Japanese woman underwent sigmoidectomy for a sigmoid colon carcinoma with multiple liver metastases. Two months after surgery, she received chemotherapy comprising hepatic arterial infusion of 5-FU. During the 2nd chemotherapy session 7 days after the first, she complained of anterior chest pain. Her electrocardiograms showed elevations of the ST segment in almost all leads, confirming the diagnosis of angina pectoris. Soon after the third chemotherapy session the same type of attack occurred again. The close association of the attacks with 5-FU administration suggested that the angina might have been induced by 5-FU. Further attacks were avoided by discontinuing the 5-FU thereafter. The incidence of cardiac toxicity 5-FU has been reported to be 1.6-7.6%. Labianca et al. found 17 cases of 5-FU-associated cardiopathy, 15 of which were angina pectoris, out of 1,083 patients treated with the drug for various kinds of neoplasm. Analysis of 6 domestic cases including ours revealed that all patient lacked a previous history of cardiac disease except one who had an arrhythmia. There seemed to be no dose-dependent correlation with 5-FU-induced angina. Cardiac events were found even in the earlier phase of chemotherapy. Since 5-FU is widely used in the treatment of a number of gastrointestinal malignancies, one should bear in mind its cardiac toxicity, manifested as angina pectoris.