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Biomedical subjects

T Kaminuma

Publications and source records attributed to T Kaminuma.

At least 19 recordsLinked to original sources

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.

Animals

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.

Cells

[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.

Databases, Factual

[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).

Accidents

[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.

Databases, Factual

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.

Cell Cycle

[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.

Drug Information Services

[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.

Computer Communication Networks

[Dissemination of the Japanese version of the International Chemical Safety Card (ICSC) on the World Wide Web (WWW)].

ge of the Japanese version of the International Chemical Safety Cards (ICSC). We prepared the Japanese text files of ICSC, converted them into HTML files and also prepared the dictionary database for the retrieval system, using programs which we developed. These programs shortened the time of work remarkably. 2D- and 3D-structures of chemicals were also incorporated in each ICSC page. Approximately 900 ICSCs in Japanese are provided at the moment on the homepage.

Computer Communication Networks

Development of calcitonin gene-related peptide slow-release tablet implanted in CSF space for prevention of cerebral vasospasm after experimental subarachnoid haemorrhage.

The calcitonin gene-related peptide (CGRP), a known potent intrinsic cerebral vasodilator, is contained in the sensory nerves from trigeminal ganglia that inervate the cerebral arteries. We previously reported that human alpha CGRP (hCGRP) dilates spastic cerebral arteries after experimental subarachnoid haemorrhage (SAH) in rabbits. In the present study, we investigated the prophylactic potential of a sustained higher cerebrospinal fluid level of hCGRP against experimental cerebral vasospasm. An hCGRP slow-release tablet (hCGRP s-r tablet) was developed for cisternal implantation. Experimental SAH was induced by percutaneous cisternal injection of autologous arterial blood. Angiography was initiated on day 1 (before SAH) and performed everyday. The hCGRP s-r tablet was implanted into the cisterna magna on day 2 in the treated groups. The spastic response of the basilar artery was maximized on day 4 in the non-treated (80.7% of day 1) and the placebo-treated (79.3%) groups. In contrast, the arterial diameters on day 4 were 96.1% and 90.5% of day 1 in the groups implanted with hCGRP 24 micrograms and 153 micrograms s-r tablets, respectively. We also measured the concentration of hCGRP in the cerebrospinal fluid (CSF) following implantation of the hCGRP 24 micrograms s-r tablet in the cisterna magna. The hCGRP concentration before implantation was below the dectable level. Following implantation, the hCGRP level in the CSF was 23.12 nmol/L on the second day and remained at elevated levels until the fifth day. These experiments suggest that the intrathecal single implantation of the hCGRP s-r tablet could produce an elevated concentration of hCGRP in the CSF over five days and have prevented the cerebral vasospasm after SAH in the rabbit. The hCGRP s-r tablet may be clinically applicable in the treatment of patients with SAH against cerebral vasospasm.

Animals

Effect of calcitonin gene-related peptide on delayed cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is an intrinsic vasodilatory substance contained in perivascular nerve fibers of intracranial arteries. It is suggested that CGRP plays a role in cerebral vasospasm after subarachnoid hemorrhage (SAH). METHOD: An experimental SAH was produced by intracisternal injection of arterial blood in rabbits. The animals were treated with intrathecal administration of CGRP solution 3 days after SAH. The degree of vasospasm and the effect of CGRP were evaluated angiographically by measuring the basilar artery diameter. RESULTS: The basilar artery constricted to 73.0% of the pre-SAH values 3 days after SAH. Fifteen minutes after injection of 10(-10) mol/kg CGRP, the basilar artery dilated to 117.1% (n = 8), which was significantly larger than 67.1% in the vehicle group (n = 8) (p < 0.01). The significant vasodilatory effect of CGRP, compared with the vehicle group, lasted for 6 hours. CONCLUSIONS: Intrathecal administration of CGRP has therapeutic potential for treating cerebral vasospasm.

Animals

Prevention of cerebral vasospasm by calcitonin gene-related peptide slow-release tablet after subarachnoid hemorrhage in monkeys.

OBJECTIVE: The goal of this work was to investigate the efficacy of a calcitonin gene-related peptide (CGRP) slow-release tablet (CGRP tablet) for the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: Experimental SAH was produced in 10 cynomolgus monkeys by placing a clot around the internal carotid artery bifurcation (Day 0). In five animals, CGRP tablets (1200 micrograms of CGRP) were then placed in the cerebrospinal fluid space (CGRP group). In two animals, placebo tablets were similarly placed (placebo group). The remaining three animals were treated with no tablets after SAH (SAH group). A series of angiographic analyses were performed, before SAH and on Days 7 and 14, to examine changes in the diameters of the ipsilateral internal carotid artery, middle cerebral artery, and anterior cerebral artery. The CGRP concentration in the cerebrospinal fluid taken before each angiogram was also determined. RESULTS: In the SAH and placebo groups, cerebral vasospasm developed on Day 7 (54.8% of the pre-SAH value at the internal carotid artery, 62.3% at the middle cerebral artery, 51.3% at the anterior cerebral artery, and 56.1% as an average of the three arteries). In the CGRP group, vasospasm was significantly ameliorated at the middle cerebral artery, at the anterior cerebral artery, and on average (81.7, 81.1, and 75.7%, P < 0.05, 0.03, and 0.02, respectively). The CGRP concentration was positive only on Day 7 for the CGRP group (6.5 nmol/L). CONCLUSION: The CGRP tablet prevented cerebral vasospasm after SAH and may have significant potential for the treatment of patients with SAH.

Animals

[NIHS information and computing infrastructure (NICI)].

We describe the information and computing infrastructure in National Institute of Health Sciences, which were constructed until May, 1996. The in house computer network and computing facilities for common usage in NIHS have been developed under the initiative of Division of Chem-Bio Informatics since 1989. The present LAN (Local Area Network) consists of coaxial cables and optic fibers which are connected by a LAN Switch. The LAN is connected to the Internet via IMnet, the inter ministry network back bone of the Science and Technology Agency. Various types of workstations and personal computers such as SUN WS, Silicon Graphics WS, IBM WS & PC, Macintosh, and NEC PC are connected to the LAN. This computing network environment which we named NICI (NIHS Information and Computing Infrastructure) not only provides network communications but also facilitates advanced computating systems for chemical safety research at NIHS as a COE.

Biological Science Disciplines

[Development of a base system for information dissemination of the Internet].

The development of information and computing infrastructure at NIHS (NICI), enabled us to provide a good environment for storing information that can be accessed by the Internet. Information can be stored either on WWW servers or on databases. All databases were developed on PC using database management systems such as 4th Dimension or Access, and were transferred to a UNIX machine with the database management system Sybase. A tool for accessing databases via the WWW (Web) was developed. This interface program used a freeware called Genera. Tools were also implemented for handling the so called VRML worlds.

Computer Communication Networks

[A structure based pharmaceutical database for drug interactions].

A structure-based pharmaceutical database for drug interactions has been developed. This database is based on the ISIS/Desktop and the Microsoft Access relational database system for Windows. Data of Japanese accepted name, molecular formula, molecular weight, CAS registry number, therapeutic category index code, structural formula, Japan ethical drugs code, side effects information, drug interactions information were taken from "Japanese Accepted Names for Pharmaceuticals 1992", "Drugs in Japan Ethical Drugs 1993" and "Drug Intelligence Reinforce".

Chemistry, Pharmaceutical

[An international exchange and dissemination of chemical safety information on the Internet].

An information system for chemical safety has been developed on the National Institute of Health Sciences (NIHS) Information and Computing Infrastructure. The system is based on client server systems on the local area network (LAN) connected to the Internet. A wide range of safety information for chemicals including foods, food additives, household goods, industrial chemicals and environmental pollutants were collected and put on the World Wide Web (WWW) server and the database management system, Sybase. In addition to original information contents, the System has links to many useful Web sites so that it functions as a global hub for chemical safety information.

Agrochemicals

[Dissemination of drug information on the Internet].

We developed the system of the guide for the drug and the relevant information by using the database on the Internet. We set up a site of drug information (Drug Info Guide). This system enabled pharmaceutical and medical staff to easily access the latest drug information. Further, we attempted to promote the exchange of the information regarding the safety and the efficacy of drugs among them.

Computer Communication Networks

N-hydroxyarylamine O-acetyltransferase of Salmonella typhimurium: proposal for a common catalytic mechanism of arylamine acetyltransferase enzymes.

Acetyl-CoA:N-hydroxyarylamine O-acetyltransferase is an enzyme involved in the metabolic activation of N-hydroxyarylamines derived from mutagenic and carcinogenic aromatic amines and nitroarenes. The O-acetyltransferase gene of Salmonella typhimurium has been cloned, and new Ames tester substrains highly sensitive to mutagenic aromatic amines and nitroarenes have been established in our laboratory. The nucleotide sequence of the O-acetyltransferase gene was determined. There was an open reading frame of 843 nucleotides coding for a protein with a calculated molecular weight of 32,177, which was close to the molecular weight of the O-acetyltransferase protein determined by using the maxicell technique. Only the residue of Cys69 in O-acetyltransferase of S. typhimurium and its corresponding residue (Cys68) in N-acetyltransferase of higher organisms were conserved in all acetyltransferase enzymes sequenced so far. The amino acid sequence Arg-Gly-Gly-X-Cys, including the Cys69, was highly conserved. A mutant O-acetyltransferase of S. typhimurium, which contained Ala69 instead of Cys69, no longer showed the activities of O- and N-acetyltransferase. These results suggest that the Cys69 of S. typhimurium and the corresponding cysteine residues of the higher organisms are essential for the enzyme activities as an acetyl-CoA binding site. We propose a new catalytic model of acetyltransferase for S. typhimurium and the higher organisms.

Acetyltransferases