1990 Fiscal Year Final Research Report Summary
Preparation of Polymer-Conjugated Bilirubin Oxidase and Treatment of Jaundice
| Project/Area Number |
01570164
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
MAEDA Hiroshi Kumamoto Univ. Med. School, Dept. Microbiol., Professor, 医学部, 教授 (90004613)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Masayuki Kumamoto Univ. Med. School, Dept. Surgery, Assist. Professor, 医学部, 助教授 (00040204)
KATSUKI Takato Kumamoto Univ. Med. School, Dept. Microbiol., Assist. Professor, 医学部, 講師 (40040191)
YAMAMOTO Tetsuro Kumamoto Univ. Med. School, Inst. Med. Genetics, Labo. Allergy, Assist. Professo, 医学部, 助教授 (60112405)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Influenza virus / Pathogenesis / Active oxygens / Free radical / Superoxide dismutase / Radical scavenger / Chronic viral hepatitis / Chronic viral diseases |
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| Research Abstract |
The purpose of the present investigation is to clarify the role of bacterial protease in the influenza infection and the detailed analysis pathogenic process in influenza infection. The protease used was obtained from Serratia marcescens as a model of bacterial infection. When mice were infected witt influenza virus, addition of the protease yielded remarkable increase (about 100 fold) of virus in the lung of the infected mice compared with those without protease. This was found as a synergistic outcome in the survival of mice ; all mice died at much accelerated rate, where about 40% died without the protease. Next question is that what is the pathogenic molecules in influenza infection ; virus itself or other indirect consequence. We focused free radical generation in the Bronchiol Alveolar Lavage Fluid (BALF). To our surprise the level of xanthiee oxidase (OX) was elevated 400 fold higher than that of control. XO is an enzyme which generate O_2^- as well as OH radicals using hypoxant
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hine or xanthine as its substrate. The level of NADPH oxidase, another source of O_2^- generation was elevated at most 7 fold in BALF. Then, we investigated upstream cascadeof hypoxanthine or xanthine generation ; which is inosine derived after deamination of adenosine by adenosine deaminase.
The adenosine deaminase activity was elevated 20 fold of uninfected mice ; a solid evidence of enhanced supply of fuel for XO. Then, we tested effect of removal of O_2^- cure 90% of virus infected mice otherwise all died. This finding was further strengthened by the fact that inhibition of XO by allopurinol was beneficial to the survival of mice. Generation of XO from xanthine dehydrogenase is mediated via serine protease which can be inhibited by soybean trypsin inhibitor. The effect of this inhibitor was found also effective to the viral infected mice for their survival. This inhibitor may be effective also inhibiting activation of virus by serine protease in BALF and also inhibiting kallikrein which generate bradykinin a major cause of vascular permeability and inflammation. Less
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