| Project/Area Number |
63570358
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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 |
Neurology
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| Research Institution | Fukushima Medical College (1989)
Tohoku University (1988) |
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Principal Investigator |
TSUKAMOTO Tetsuro Fukushima Medical College, Dept Neurology, Assist Prof., 神経内科, 講師 (20171978)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIE Osamu Shionogi Co., Director, 研究部, 部長 (10166910)
YAMAMOTO Teiji Fukushima Medical College, Dept Neurology, Prof., 神経内科, 教授 (10106487)
IWASAKI Yuzo Tohoku Uni Sch Med., Dept Neurol Sci., Prof., 医学部・病態神経学, 教授 (00142927)
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| Project Period (FY) |
1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Paraneoplastic cerebellar degeneration / Antineural autoantibody / Malignant tumor / Anti-Purkinje cell antibody / cDNA cloning |
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| Research Abstract |
We studied serum autoantibodies from six patients with paraneoplastic cerebellar degeneration using rat brains. Immunohistochemically, serum samples from four of six patients with uterine or overian tumors showed a similar staining pattern, labeling Purkinje cells and various other neurons distributed throughout the brain and spinal cord. The immunoblot study showed that these serum samples recognized the common 52- kd band. Serum from a patient with duct carcinoma of the breast reacted with the 46- kd band with a similar but weaker immunohistochemical reactivity. Serum from another patient with small-cell carcinoma of the lung in whom paraneoplastic cerebellar degeneration and Eaton-Lambert myasthenic syndrome developed recognized the 40-kd and 38-kd bands with a different imunostaining pattern. Autoantibodies in patients with paraneoplastic cerebellar degeneration are directed to a variety of neuronal antigens that may differ from patient to patient.
We isolated a cDNA clone encoding
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a 52-kd protein recognized by an anti-Purkinje cell antibody in the serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. The recombinant protein expressed in prokaryotic cells was specifically recognized by the anti-Purkinje cell antibody from the patient and its molecular weight was identical with that of antigenic protein in the cerebellum. The deduced protein consisted of 450 amino acids dominated by hydro- philic residues, the calculated relative molecular mass was 51238 and the predicted value of the isoelectric point was 4.99. This cDNA sequence and the deduced protein sequence have not been reported previously and showed no homologies with the cDNA or the amino acid sequences in the GenBank, EMBL or NBRF databases, including the cDNA for a 34-kd cerebellar protein (CDR34) which is recognized by an anti-Purkinje cell antibody. Unexpectedly, the transcript of this gene was detected not only in the cerebellum and the brain stem, but also in an extraneural tissue, the intestine. Less
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