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Biomedical subjects

T Hirata

Publications and source records attributed to T Hirata.

576 records · Page 32Linked to original sources
PubMedDate not supplied

Development and utilization of a drug information system in the Japanese pharmaceutical industry.

Pharmaceutical companies are responsible for providing updated, relevant information on the efficacy, safety and quality of drugs to medical professionals and finally to patients. To fulfill this responsibility, we must always endeavour to collect and evaluate the relevant information. We developed a drug information database system called Advanced Medical Online Network of Daiichi (AMOND) to manage various information generated during development of new products and after launch of the products using the classification format for retrieval. This system has been used for 9 years for the purpose of supporting medical representatives who play a primary role in the drug information services in the pharmaceutical industry. This system is incorporated into an on-line network system, and can be directly accessed by more than 1200 people at 11 branch offices and more than 110 subbranches all over the country. We upgraded this system to AMOND-II to improve the function, including retrieval and output abilities. As a result, utilization by users of this system increased six times. We report on the improved system, AMOND-II and our experience of the system.

Data Collection↗
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ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients.

OBJECTIVE: Methotrexate (MTX) is most widely used for the treatment of rheumatoid arthritis (RA). However, it has certain drawbacks with regard to individual differences in its therapeutic effects as well as the differences in the patients' response to MTX therapy. We investigated whether multi-drug resistance-1 (ABCB1) C3435T, reduced folate carrier-1 (RFC1) G80A, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) C347G and a 6bp-deletion polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS) gene are predictive of MTX sensitivity and its adverse effects. METHODS: Patients whose last maintenance dosage of MTX was 6 mg/week or those in whom MTX therapy was changed due to poor response to MTX were regarded as non-responders. The data of 124 RA patients who had received MTX treatment were retrospectively analyzed for polymorphisms in the ABCB1, RFC1, ATIC and TYMS genes, MTX sensitivity and MTX toxicity. RESULTS: There were no significant differences in MTX sensitivity among the genotypes of RFC1, ATIC and TYMS genes. ABCB1 3435TT cases included statistically significantly more non-responders than 3435CC cases according to univariate analysis (crude odds ratio (OR) = 8.91, p = 0.001) and multivariate analysis (adjusted OR = 8.78, p = 0.038). There were no significant differences in MTX toxicity among the genotypes of all the genes. CONCLUSION: These results suggested that the genetic diagnosis of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of RA patients. However, further pharmacokinetics studies are required in this regard.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Electron microscopic observations of cell division in Mycobacterium leprae by means of serial ultrathin sectioning.

The division of Mycobacterium leprae in human skin was studied in the ultrathin sections at the electron microscopic level. A few dividing bacilli were observed. The division seemed to be accomplished by inward extension ob both the cell wall and the cytoplasmic membrane into the cytoplasm of the bacillary cell to form a septum. The intracellular membranous organelle (mesosome) is assumed to play a role in division.

Cell Division↗
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Electron microscopic observations of intracytoplasmic membranous structures in Mycobacterium leprae by means of serial ultrathin sectioning.

The fine structures and interconnections between the cytoplasmic membrane and mesosomes of Mycobacterium leprae in human skin were studied in ultrathin sections. These intracellular membranous organelles were seen as laminated structures and as clusters of vesicles, which were trilaminar consisting of two electron-dense layers separated by an electron-transparent zone. The formation of mesosomes seems to be initiated by invagination and/or folding of the cytoplasmic membrane.

Cell Membrane↗
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Combined therapy with FK-506 and cyclosporine for canine lung allotransplantation: immunosuppressive effects and blood trough levels.

The therapeutic and adverse effects of FK-506 and cyclosporine used in combination were examined in 35 adult mongrel dogs with allotransplantation of the left lung. The experimental animals were allocated to six groups: group A, optimal dose of FK-506 (n = 5, FK-506 0.1 mg/kg/day, intramuscularly); group B, optimal dose of cyclosporine, (n = 5, cyclosporine 20 mg/kg/day, by mouth); group C (n = 5, FK-506 0.03 mg/kg/day, intramuscularly); group D (n = 5, cyclosporine 6 mg/kg/day, by mouth); group E (n = 5, FK-506 0.03 mg/kg/day+cyclosporine 6 mg/kg/day); and group F (n = 10, FK-506 0.05 mg/kg/day+cyclosporine 10 mg/kg/day). The animals were killed on postoperative day 28 or when extreme deterioration had developed. In groups C and D, the grafts underwent moderate to severe rejection. The treatment in group E resulted in insufficient immunosuppression, although additional effect was noted. The rejection was suppressed at least as strongly in group F as in groups A and B. One death occurred in each of groups A and F from hematemesis. The blood concentrations of FK-506 and cyclosporine in group E were not higher than in groups C and D. The whole blood concentrations of FK-506 deviated less, and they were superior to the serum concentrations as a monitor. The combination of FK-506 and cyclosporine at one half of their optimal doses suppressed the rejection almost completely and did not increase the adverse effects.

Animals↗
PubMedDate not supplied

Therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in gastric cancer.

The therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in 64 inoperable gastric cancer patients are reported. An intermediate-dose treatment was given to 48 patients, and a low-dose treatment to 16 patients. In the intermediate-dose treatment, leukopenia was observed in 11 patients, nausea and vomiting in six patients and diarrhea and stomatitis in two patients each. In the low-dose treatment, no patient developed toxic symptoms of grade 3 or 4. All 9 responders had adenocarcinoma of the poorly differentiated type and the response rate in patients who belonged to this type was 32.1%.

Adult↗
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Molecular characterization of a dominantly inherited bleeding disorder with impaired platelet responses to thromboxane A2.

Thromboxane A2 (TXA2) is a major arachidonic acid metabolite of platelets and induces platelet functions by binding to specific receptors on the membrane. We have found patients with hemostatic defects due to impaired platelet responses to TXA2, and molecular characterization of the patients has been carried out. Platelets from these two unrelated patients showed impaired aggregation responses to TXA2 and its analogues despite the normal response to thrombin. Although the patients' platelets exhibited normal binding activities to TXA2 analogues, they showed decreased GTPase activity and second messenger formation when stimulated by STA2, a stable TXA2 agonist. To understand the molecular basis of this abnormality, we determined the cDNA sequence of the TXA2 receptor by reverse transcription-polymerase chain reaction (RT-PCR) from the patient's platelet RNA, and identified a single amino acid substitution (Arg60 for Leu) in the first cytoplasmic loop of the receptor. This mutation was found in both isoforms of the platelet TXA2 receptor which we have recently found: TXR alpha with the same structure as the placental TXA2 receptor and TXR beta with the same structure as the endothelial TXA2 receptor, and was detected exclusively in affected members of two unrelated families with the disorder. The mutant TXR alpha and TXR beta expressed in COS-m6 cells showed decreased agonist-induced phospholipase C activation despite their normal ligand binding affinities. These results suggest that the Arg60 for Leu mutation is responsible for the disorder and imply a critical role for the first cytoplasmic loop in the interaction of the TXA2 receptor with the G protein.

Base Sequence↗
PubMedDate not supplied

Prevention of postoperative pericardial adhesions with a defibrinogenating agent.

Pericardial adhesions pose a major problem during re-operative cardiac surgical procedures. The purpose of this study was to determine the effect of Batroxobin, a fibrinogen depleting agent, on the incidence of experimental pericardial adhesions. Twenty-four rabbits were divided into 3 groups of 8 rabbits each and pericardial mesothelial injury was induced by abrasion. Group A included rabbits receiving no further treatment, Group B included rabbits receiving intrapericardial injection of Ringer's solution, and Group C included rabbits receiving intrapericardial injection of Batroxobin. Three weeks after surgery, the incidence of adhesions in Groups B and C was compared with that in Group A. Pericardial adhesions found in 80% of the rabbits in Groups A and B. However, only 14% of the rabbits in Group C had pericardial adhesions (p < 0.05). Our findings demonstrated that intrapericardial Batroxobin reduced the incidence of pericardial adhesions in an animal model.

Animals↗