Plastic resin pellets as a transport medium for toxic chemicals in the marine environment.

Plastic resin pellets (small granules 0.1-0.5 centimeters in diameter) are widely distributed in the ocean all over the world. They are an industrial raw material for the plastic industry and are unintentionally released to the environment both during manufacturing and transport. They are sometimes ingested by seabirds and other marine organisms, and their adverse effects on organisms are a concern. In the present study, PCBs, DDE, and nonylphenols (NP) were detected in polypropylene (PP) resin pellets collected from four Japanese coasts. Concentrations of PCBs (4-117 ng/g), DDE (0.16-3.1 ng/g), and NP (0.13-16 microg/g) varied among the sampling sites. These concentrations were comparable to those for suspended particles and bottom sediments collected from the same area as the pellets. Field adsorption experiments using PP virgin pellets demonstrated significant and steady increase in PCBs and DDE concentrations throughout the six-day experiment, indicating that the source of PCBs and DDE is ambient seawater and that adsorption to pellet surfaces is the mechanism of enrichment. The major source of NP in the marine PP resin pellets was thought to be plastic additives and/or their degradation products. Comparison of PCBs and DDE concentrations in mari

Modeling of signaling pathways for endocrine disruptors.

The so called endocrine disruptors have become an important working hypothesis for a wide range of toxicology researchers. This hypothesis has also attracted those who have worked on designer estrogens or selective estrogen receptor modulators. Already numbers of substances have been identified as such chemicals, but there remain a large number of chemicals waiting to be tested for their endocrine modulating capabilities. Because of the time and costs required for wet lab tests, it is unrealistic to apply these kinds of tests to all such suspicious or probable chemicals. Thus some theoretical methods must be developed for this purpose. However the conventional QSAR (quantitative structure activity relationships) approach is of limited relevance to this problem, because these methods do not take detailed mechanisms of molecular interactions in biological systems into account. Thus we have developed a database complex system that enables one to trace molecular interactions triggered by interaction of receptors with xenobiotic chemicals. The main components of this database complex are a potential endocrine disruptor database, a receptor database, a cell signaling networks database, a transcription factor database, and an affinity binding database based on modes of actions.

[The status of NIHS Information and Computing Infrastructure (NICI)].

From 1999 to 2000, NIHS Information and Computing Infrastructure (NICI) were newly renovated. The purposes of the renovation are (1) the improvement of the communication for business works in NIHS, (2) supporting for the research, (3) supporting for the administration work. The Internet connection speed was upgraded from 256 Kbps to 1.5 Mbps. The high quality network sever machines and database server machines were installed. The large-scale software systems were renewed their versions. Four experimental stations for medical plants at Hokkaido, Izu, Wakayama and Tanegashima connected to NIHS at Tokyo or Osaka branch by ISDN. We describe the providing information on NIHS home page, and how to utilize NICI for our research and official works.

[Development of research support environment for molecular pharmacology and toxicology].

The Chem-Bio Informatics division has developed the institute-wide computer network which is connected to the Internet via IMnet (Inter Ministry Network) sponsored by the Government. We call the network and associated information and computing infrastructure as NICI, the NIHS Information and Computing Infrastructure. The primary goal of NICI is to provide general communication environment such as e-mails, and the second goal is to provide WWW environment. Accomplishing these two goals the division is now challenging to develop information and computing environment that directly supports pharmaceutical and toxicological research. The prototype of this environment which consists of various chemical and biomolecular databases and computing tools has been developed under the name of MOBI-DICS. The concept and vision on how to extend the prototype to institute-wide infrastructure was discussed.

[Studies on poisonings and incidents caused by chemicals in Japan].

The criminal cases of poisonings caused by poisonous, deleterious or other hazardous chemicals in Japan were studied. The data (111 cases) were collected mainly from the newspaper database (Aug. 1984-Feb. 1999). More than half cases were caused by chemicals which are regulated by the "Poisonous and Deleterious Substance Control Law". Copy-cat poisonings occurred in succession in 1984-1985 and 1998. Many cases occurred at the laboratories of institutes and universities, and hospitals where there are various kinds of chemical reagents. The cases of chemical incidents such as those which occurred while transportation were also discussed.

[Development of domain specific search engines].

As cyber space exploding in a pace that nobody has ever imagined, it becomes very important to search cyber space efficiently and effectively. One solution to this problem is search engines. Already a lot of commercial search engines have been put on the market. However these search engines respond with such cumbersome results that domain specific experts can not tolerate. Using a dedicate hardware and a commercial software called OpenText, we have tried to develop several domain specific search engines. These engines are for our institute's Web contents, drugs, chemical safety, endocrine disruptors, and emergent response for chemical hazard. These engines have been on our Web site for testing.

[Archives of environmental health digital maps and their delivery by the Internet].

Geographic Information System is becoming a very important tool for environmental health research. We have produced various digital maps for different scales for different purposes. The burst of E. Coli O-157, distribution of hazadarous chemicals in East Asia, and coastal resin pellets are some examples. It now becomes a problem how to archive these digital maps and how to retrieve these maps according to user's request. We have developed a computer system that can store various types of digital maps and can retrieve them from WWW client machines. The key concept of this archive system is to classify every digital maps according to their region of interest.

[Distribution and origin of plastic resin pellets as environmental pollutants at the East China Sea area].

Plastic debris are important marine pollutants. Plastic debris consist of resin pellets and waste plastics. We are particularly interested in resin pellets. We made field survey of resin pellets at nearly 400 sites in 200 beaches in Japan and neighboring countries. The pellets were found at all most all Japan coasts we surveyed and at some beaches of Macao, Hong Kong, Xiamen, the north of Taipei, and Cheju Island in Korea. The number of pellets was more than 1000 pieces per m2 on the most abundant beach in Japan. Through further analysis using GC/ECD, endocrine disrupting chemicals, PCBs, DDTs, HCHs and Nonylphenol were detected in selected samples. Biota such as Bryozoa were observed on the surface of pellets washed up on the beaches in subtropical areas. Pellets has been suspected to affect wildlife and human health, but we have no report on affection to human.

Development of the receptor database (RDB): application to the endocrine disruptor problem.

MOTIVATION: To represent various aspects of receptors effectively, we developed the receptor database (RDB), using an object-oriented database management system ACEDB and the Internet/WWW technology. RESULTS: RDB was constructed so that the system collects data items such as attributes of proteins from distributed data sources of the Internet, and so that it provides various viewing tools effectively, depending on different types of receptor data. Such sources include standard international biological databases such as the up-to-date database of PIR, Swiss Prot, PDB, GenBank and GDB. Application to the endocrine disruptor problem is presented. AVAILABILITY: RDB is available through the Internet at http://impact.nihs.go.jp/RDB.html.

A pathway finding system for the cell signaling networks database.

We report on a knowledge-based pathway-finding system that builds on the cell-signaling networks database, CSNDB, which we developed previously. This new system, PaF-CSNDB, uses a general inference engine to apply rules for finding and coupling pathways between or around specific biomolecules from the CSNDB database. We show how PaF-CSNDB finds relationships in a large but fragmented collection of cell-signaling knowledge by filtering out and composing together those sections of pathways specified from an extensive and complex set of binary or pair-wise cell-signaling reactions.

[Preparation of the database and the Internet (WWW) homepage for regulations on chemicals in Japan].

We prepared a database on chemical regulations in Japan. The regulations consist of "The Law concerning the Examination and Regulation of Manufacture, etc., of Chemical Substances", "Poisonous and Deleterious Substances", Control Law", "Waterworks Law", "Law for the Control of Household Products containing Harmful Substances", and Pesticide Residues in Food Sanitation Law". We also set up a World Wide Web (WWW) homepage containing an explanation of the law as well as chemical names, CAS registry numbers, and standards. The WWW pages contain lists of chemicals and the retrieval page for the database.

Prevention of cerebral vasospasm by vasodilatory peptide maxadilan following subarachnoid hemorrhage in rabbits.

Maxadilan is a vasodilatory peptide isolated from the blood-feeding sand fly Lutzomyia longipalpis. Its vasodilatory activity, estimated by the formation of erythema on rabbit skin, is greater than those of calcitonin gene-related peptide, vasoactive intestinal polypeptide and pituitary adenylyl cyclase activating polypeptide (PACAP). We have recently demonstrated that maxadilan is a specific agonist for the PACAP type I receptor, which is widely distributed in brain. Therefore, we were interested in the vasodilatory effect of maxadilan on cerebral arteries and the possibility of its clinical use for the delayed cerebral vasospasm following subarachnoid (SAH). In the first experiment, 10(-10) mol/kg of maxadilan (in sterile water) was injected into the cisterna magna three days after the induction of experimental SAH in rabbits (n = 6). Maxadilan dilated spastic basilar arteries within 30 min of the injection, but not at 6 h. In the second experiment, to prolong the vasodilatory effect of maxadilan, tablets containing stearic acid, hydrogenated oil, lactose, hydroxypropylcellulose and 15 mg of maxadilan were prepared. In vitro testing showed that 60% of maxadilan could be released slowly within the initial five days. In vivo experiments were performed to implant the maxadilan tablet (n = 7) and the placebo tablet (n = 6) into the cisterna magna after the induction of experimental SAH in rabbits. The spastic response of the basilar artery was maximum on day three in the placebo-treated groups. In contrast, we observed no significant change in the arterial diameter until day five in the rabbits treated with maxadilan tablet. These data suggest that maxadilan may have therapeutic potency in treating cerebral vasospasm.

[Development of NIHS Information and Computing Infrastructure (NICI)].

We describe the development of NICI, which we extended during June 1996 to May 1998. The direct lines between our Experimental Stations for Medicinal Plants at Tsukuba and Tsukuba Node for Inter Ministry Network, and newly opened Pharmaceuticals and Medical Devices Evaluation Center at Minato-ku and NIHS at Setagaya-ku in Tokyo, were constructed. Although the main frame in NIHS at Setagaya is not different since May 1996, we provided many databases and useful information on Drugs, Foods and Chemicals, constructing the interface between World Wide Web and databases. Our Home Page was timely updated.

[Preparation of the database and the homepage on chemical accidents relating to health hazard].

We collected the data on accidents due to chemicals occurred in Japan, and prepared the database. We also set up the World Wide Web homepage containing the explanation on accidents due to chemicals and the retrieval page for the database. We designed the retrieval page so that users can search the data from keywords such as chemicals (e.g. chlorine gas, hydrogen sulfide, pesticides), places (e.g. home, factory, vehicles, tank), causes (e.g. reaction, leakage, exhaust gas) and others (e.g. cleaning, painting, transportation).

[Dissemination of drug information by the Internet].

We reported a system for dissemination of the drug information and its related subjects through the Internet (Drug Info Guide) in Bull. Natl. Inst. Health Sci. 1996. Since then, further information were added in the system. These include the web site for ICH Guideline in Japanese and English, and Australasian Cochrane Centre mirror site. Furthermore, the titles and their abstracts which were reviewed by Cochrane groups in Cochrane Library were translated in Japanese, and these information together with the search guide for useful resource regarding the drug information were also presented on WWW.

A database for cell signaling networks.

We developed a data and knowledge base for cellular signal transduction in human cells, to make this rapidly growing information available. The database includes all the biological properties of cellular signal transduction, including biological reactions that transfer cellular signals and molecular attributes characterized by sequences, structures, and functions. Since the database is based on the object-oriented technique, highly flexible methods of data definition and modification are necessary to handle this diverse and complex biological information. The database includes attractive graphical representations of signaling cascades and the three-dimensional structure of molecules. The database is a novel application of ACEDB, which was the database originally developed to store the C. elegans genome. The database can be accessed through the Internet at http://geo.nihs.go.jp/csndb.html.

Development of a cell signaling networks database.

In multicellular organisms cell signaling networks play important roles in wide range of biological phenomena, such as development, differentiation, reproduction, morphogenesis, carcinogenesis, apoptosis, and even learning. In order to explain biological phenomena based on cell signaling models, we have developed a database for cell signaling networks. The system contains mechanisms of signal transduction and structure and functional data and references of extracellular chemicals and biomolecules. CSNDB is constructed using ACEDB system, and includes various graphical representations such as pathway diagrams, map diagrams, 3-D images, pictures, and VRML environment. The system will be useful for modeling cells and their information processing, and to explain important biological phenomena based on these models.

[Building information infrastructure at research institutions that support health hazard control].

In recent years the Ministry of Health and Welfare (MHW) encountered large scale health hazards and medicare incidents that required flexible, intersectional, and dynamic responses. Both research institutions under the MHW and their researchers got involved in project teams which were organized in order to cope these hazards and incidents. However it might be more effective if some information infrastructure for hazard control is built as one component of the MHW hazard management system. In this paper the design concept and implementation for such information infrastructure were discussed. The infrastructure consists of computer networks and systems which are based on the Internet and the related technologies such as WWW.

[Development of a geographical information system and its application to Escherichia coli O-157 patient distribution].

The so called Geographical Information System (GIS) is one of the basic tools for wide range of public health applications. We had developed a general purpose GIS and applied it to represent geographical distribution of patients of the bacterium E. coli O-157 which bursted out in Japan last early summer particularly at Sakai City in Osaka Prefecture. The patient record have been supplied from the Food Safety Office of the Ministry of Health and Welfare. These records were handled by EXCEL. The basic geographical data was constructed from the map data provided by Japan Geographical Survey Institute, and ArcView 2 was used as the map system. The maps were converted to Graphics Interchange Format (GIF) files and put on our Web server.