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  • 1990-1994  (142,990)
  • 1985-1989  (31)
  • 1990  (142,990)
Material
Years
Year
Language
  • 1
    Book
    Book
    Wien [u.a.] :Springer, ; 1.1977 - 16.2003; damit Ersch. eingest.
    Title: Computing : archives for informatics and numerical computation; Supplementum
    Publisher: Wien [u.a.] :Springer,
    Year of publication: 1977-2003
    Dates of Publication: 1.1977 - 16.2003; damit Ersch. eingest.
    Type of Medium: Book
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  • 2
    Journal/Serial
    Journal/Serial
    New York, NY :ACM, ; 1.1969 - 7.1975/76; N.S. 1.1976 - 21.2001,1; damit Ersch. eingest.
    Title: SIGBIO newsletter /
    Author: Association for Computing Machinery / Special Interest Group on Biomedical Computing
    Publisher: New York, NY :ACM,
    Year of publication: 1969-2001
    Dates of Publication: 1.1969 - 7.1975/76; N.S. 1.1976 - 21.2001,1; damit Ersch. eingest.
    ISSN: 0163-5697
    Type of Medium: Journal/Serial
    Language: Undetermined
    Parallel Title: Internetausg. ---〉:Biomedical computing
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  • 3
    Journal/Serial
    Journal/Serial
    New York, NY :North-Holland, ; 1.1984 - 46.2000
    Title: ¬The¬ journal of logic programming
    Publisher: New York, NY :North-Holland,
    Year of publication: 1984-2000
    Dates of Publication: 1.1984 - 46.2000
    ISSN: 0743-1066
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:¬The¬ journal of logic and algebraic programming
    Parallel Title: Internetausg. ---〉:¬The¬ journal of logic and algebraic programming
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  • 4
    Journal/Serial
    Journal/Serial
    Amsterdam :CWI, ; 1.1988 - 12.1999; damit Ersch. eingest.
    Title: CWI quarterly
    Author: Centrum voor Wiskunde en Informatica 〈Amsterdam〉
    Publisher: Amsterdam :CWI,
    Year of publication: 1988-1999
    Dates of Publication: 1.1988 - 12.1999; damit Ersch. eingest.
    ISSN: 0168-826X , 0922-5366
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Centrum voor Wiskunde en Informatica 〈Amsterdam〉: CWI newsletter
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  • 5
    Book
    Book
    New York, NY :ACM, ; Nachgewiesen 2.1971 - 20.1999,4; damit Ersch. eingest.
    Title: Computer personnel : a quarterly publ. of the Special Interest Group on Computer Personnel Research, SIGCPR
    Publisher: New York, NY :ACM,
    Year of publication: 1971-1999
    Dates of Publication: Nachgewiesen 2.1971 - 20.1999,4; damit Ersch. eingest.
    ISSN: 0160-2497
    Type of Medium: Book
    Parallel Title: Internetausg. ---〉:Computer personnel
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  • 6
    Title: SIGART bulletin : a quarterly publ. of the Special Interest Group on Artificial Intelligence
    Author: Association for Computing Machinery / Special Interest Group on Artificial Intelligence
    Publisher: New York, NY :ACM,
    Year of publication: 1990-1998
    Dates of Publication: 1.1990 - 9.1998
    ISSN: 1053-4830
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Association for Computing Machinery / Special Interest Group on Artificial Intelligence: SIGART newsletter
    Subsequent Title: Forts. ---〉:Intelligence
    Parallel Title: Internetausg. ---〉:Artificial intelligence
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  • 7
    Journal/Serial
    Journal/Serial
    New York, NY :ACM, ; 4.1969 - 33.1998,2; damit Ersch. eingest
    Title: SIGNUM newsletter
    Author: Association for Computing Machinery / Special Interest Group on Numerical Mathematics
    Publisher: New York, NY :ACM,
    Year of publication: 1969-1998
    Dates of Publication: 4.1969 - 33.1998,2; damit Ersch. eingest
    ISSN: 0163-5778
    Type of Medium: Journal/Serial
    Former Title: Vorg. ---〉:Association for Computing Machinery / Special Interest Committee on Numerical Mathematics: SICNUM newsletter
    Additional Information: 16,3=3,2 von:Association for Computing Machinery / Technical Committee on Fortran: FORTEC forum
    Parallel Title: Internetausg. ---〉:Numerical mathematics
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  • 8
    Journal/Serial
    Journal/Serial
    Woodbury, NY :AIP, ; 1.1987,1(Nov./Dez.); 2.1988 - 12.1998
    Title: Computers in physics /
    Contributer: American Institute of Physics
    Publisher: Woodbury, NY :AIP,
    Year of publication: 1987-1998
    Dates of Publication: 1.1987,1(Nov./Dez.); 2.1988 - 12.1998
    ISSN: 0894-1866
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:Computing in science & engineering
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  • 9
    Journal/Serial
    Journal/Serial
    San Francisco, Calif. :Miller Freeman, ; 1.1983 - 16.1998,3
    Title: Unix review : the publication for the Unix community
    Publisher: San Francisco, Calif. :Miller Freeman,
    Year of publication: 1983-1998
    Dates of Publication: 1.1983 - 16.1998,3
    ISSN: 0742-3136
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:Unix review's performance computing
    Parallel Title: Internetausg. ---〉:Unix review.com
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  • 10
    Journal/Serial
    Journal/Serial
    Amsterdam [u.a.] :Elsevier [u.a.], ; 9.1985 - 30.1998
    Title: Computer networks and ISDN systems : the international journal of computer and telecommunications networking
    Publisher: Amsterdam [u.a.] :Elsevier [u.a.],
    Year of publication: 1985-1998
    Dates of Publication: 9.1985 - 30.1998
    ISSN: 0169-7552 , 0376-5075
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Vorg. u. Forts. ---〉:Computer networks
    Note: Computer networks for research in Europe
    Additional Information: In 14,1=15 von:Networkshop: Conference report
    Additional Information: 16,1/2=4; 17,4/5=5 von:European Networkshop: European Networkshop
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  • 11
    Journal/Serial
    Journal/Serial
    Amsterdam :Amsterdam Universities Computing Centre, ; Nr. 1.1984 - 69.1997; damit Ersch. eingest.
    Title: Supercomputer : bimonthly magazine on supercomputing in the Netherlands
    Publisher: Amsterdam :Amsterdam Universities Computing Centre,
    Year of publication: 1984-1997
    Dates of Publication: Nr. 1.1984 - 69.1997; damit Ersch. eingest.
    ISSN: 0168-7875
    Type of Medium: Journal/Serial
    Language: Undetermined
    Note: Teils auch mit Jg.-Zählung
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  • 12
    Journal/Serial
    Journal/Serial
    Thousand Oaks, Calif. :Sage Science Press, ; 1.1987 - 11.1997
    Title: ¬The¬ international journal of supercomputer applications and high performance computing
    Publisher: Thousand Oaks, Calif. :Sage Science Press,
    Year of publication: 1987-1997
    Dates of Publication: 1.1987 - 11.1997
    ISSN: 1078-3482 , 0890-2720
    Type of Medium: Journal/Serial
    Subsequent Title: Forts. ---〉:¬The¬ international journal of high performance computing applications
    Parallel Title: Internetausg. ---〉:¬The¬ international journal of high performance computing applications
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  • 13
    Book
    Book
    Bergheim :DATACOM-Zeitschriften-Verl., | Köln Müller -1993,9 ; 11.1973 - 14.1976; 19.1981 - 20.1982; 1983 - 1994; 32.1995 - 34.1997,10
    Title: Online : erfolgreiches Informationsmanagement, ADI-Nachrichten, ÖVD ; Organ d. ADI - Anwenderverband Deutscher Informationsverarbeiter e.V
    Contributer: Anwenderverband Deutscher Informationsverarbeiter
    Publisher: Bergheim :DATACOM-Zeitschriften-Verl., , Köln Müller -1993,9
    Year of publication: 1973-1997
    Dates of Publication: 11.1973 - 14.1976; 19.1981 - 20.1982; 1983 - 1994; 32.1995 - 34.1997,10
    ISSN: 0340-1545 , 0179-6623 , 0342-9393
    Type of Medium: Book
    Language: Undetermined
    Former Title: Vorg. ---〉:Zeitschrift für Datenverarbeitung
    Subsequent Title: 15.1977 - 18.1980 ---〉:ADL-Verband für Informationsverarbeitung: ADL-Nachrichten, Online
    Subsequent Title: Aufgeg. in ---〉:Information week
    Note: Später ohne Zählung
    Additional Information: Beil. ---〉:Drucker spezial
    Additional Information: Beil. ---〉:Online / special
    Additional Information: Darin ---〉:Anwenderverband Deutscher Informationsverarbeiter: ADI-Nachrichten, ÖVD
    Additional Information: Beil. ---〉:Pro info
    Additional Information: Beil. ---〉:Online-Info
    Additional Information: 1996 darin ---〉:Datacom-Special
    Parallel Title: 19.1981 auch in ---〉:Öffentliche Verwaltung und Datenverarbeitung
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  • 14
    Title: LISP and symbolic computation : an internat. journal ; a forum for current and envolving symbolic computing, focusing on LISP and object-oriented programming
    Publisher: Dordrecht [u.a.] :Kluwer Acad. Publ.,
    Year of publication: 1988-1997
    Dates of Publication: 1.1988 - 10.1997
    ISSN: 0892-4635
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:Higher order and symbolic computation
    Parallel Title: Internetausg. ---〉:Higher-order and symbolic computation
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  • 15
    Journal/Serial
    Journal/Serial
    Minneapolis, Minn. :Cray Research, Inc., ; Nachgewiesen 6.1984 - 18.1996,2; damit Ersch. eingest.
    Title: Cray channels : a Cray Research, Inc. publication
    Contributer: Cray Research, Inc. 〈Mendota Heights, Minn.〉
    Publisher: Minneapolis, Minn. :Cray Research, Inc.,
    Year of publication: 1984-1996
    Dates of Publication: Nachgewiesen 6.1984 - 18.1996,2; damit Ersch. eingest.
    Type of Medium: Journal/Serial
    Language: Undetermined
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  • 16
    Journal/Serial
    Journal/Serial
    München :Hanser, ; 1.1983 - 14.1996,6
    Title: Unix mail : Europas erster Informationsdienst für Unix-Hersteller und -Anwender
    Publisher: München :Hanser,
    Year of publication: 1983-1996
    Dates of Publication: 1.1983 - 14.1996,6
    ISSN: 0176-8654
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:¬Die¬ blauen Blätter
    Parallel Title: CD-ROM-Ausg. ---〉:Unix mail, die blauen Blätter
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  • 17
    Title: Nachrichtentechnische Zeitschrift : NTZ ; Zeitschrift für Informationstechnik u. Telekommunikation ; Organ der Nachrichtentechnischen Gesellschaft im VDE
    Contributer: Nachrichtentechnische Gesellschaft / Fachausschuß Informationsverarbeitung
    Publisher: Berlin :VDE-Verl.,
    Year of publication: 1955-1995
    Dates of Publication: 8.1955,10 - 40.1987,2; 40.1987,6 - 48.1995,2
    ISSN: 0027-707X
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Fernmeldetechnische Zeitschrift
    Subsequent Title: 40.1987,3-5 u. Forts. ---〉:NTZ
    Note: Mikro-Elektronik
    Additional Information: Beih. ---〉:Nachrichtentechnische Fachberichte
    Additional Information: Index 1/10=11 von:Nachrichtentechnische Fachberichte
    Parallel Title: CD-ROM-Ausg. 1994 - 1995 ---〉:Elektronisches Zeitschriftenarchiv
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  • 18
    Journal/Serial
    Journal/Serial
    Stuttgart :IBM, ; 22.1972,Apr. - 45.1995 = Nr. 210-323; damit Ersch. eingest.
    Title: IBM-Nachrichten /
    Author: IBM Deutschland GmbH 〈Stuttgart〉
    Publisher: Stuttgart :IBM,
    Year of publication: 1972-1995
    Dates of Publication: 22.1972,Apr. - 45.1995 = Nr. 210-323; damit Ersch. eingest.
    ISSN: 0018-8662
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Internationale Büro-Maschinen-Gesellschaft Deutschland 〈Sindelfingen〉: IBM-Nachrichten
    Additional Information: Beil. ---〉:Hollerith-Mitteilungen
    Parallel Title: CD-ROM-Ausg. ---〉:IBM Deutschland GmbH 〈Stuttgart〉: IBM-Nachrichten
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  • 19
    Journal/Serial
    Journal/Serial
    Oxford [u.a.] :Pergamon Press, ; 1.1960 - 19.1995
    Title: Annual review in automatic programming
    Publisher: Oxford [u.a.] :Pergamon Press,
    Year of publication: 1960-1995
    Dates of Publication: 1.1960 - 19.1995
    ISSN: 0066-4138
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:Annual reviews in control
    Additional Information: 1=3; 2=6, 3=11, 4=12; 5=13,2 von:International tracts in computer science and technology and their application
    Additional Information: 8=7; 9,2/3=8; 10=10; 11=11; 13,1=13; 14,1=15 von:Real time programming
    Additional Information: 12,1-12,2=2 von:Systems analysis and simulation
    Additional Information: 13,2=5 von:Control applications of nonlinear programming and optimization
    Parallel Title: Internetausg. ---〉:Annual reviews in control
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  • 20
    Journal/Serial
    Journal/Serial
    Baltimore, Md., ; 1.1989 - 7.1995
    Title: ORSA journal on computing /
    Author: Operations Research Society of America
    Publisher: Baltimore, Md.,
    Year of publication: 1989-1995
    Dates of Publication: 1.1989 - 7.1995
    ISSN: 0899-1499
    Type of Medium: Journal/Serial
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  • 21
    Journal/Serial
    Journal/Serial
    New York, NY :ACM Inc., ; 1.1987/88 - 4.1990/91; 5.1992; 6.1992/93; 7.1994 - 8.1995,2; damit Ersch. eingest.
    Title: LISP pointers /
    Publisher: New York, NY :ACM Inc.,
    Year of publication: 1987-1995
    Dates of Publication: 1.1987/88 - 4.1990/91; 5.1992; 6.1992/93; 7.1994 - 8.1995,2; damit Ersch. eingest.
    ISSN: 1045-3563
    Type of Medium: Journal/Serial
    Note: Special Interest Group on Programming Languages (SIGPLAN)
    Parallel Title: Internetausg. ---〉:Association for Computing Machinery / Special Interest Group on Programming Languages: ACM SIGPLAN LISP pointers
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  • 22
    Journal/Serial
    Journal/Serial
    Heidelberg :Physica-Verl., ; 16.1972 - 42.1995
    Title: Zeitschrift für Operations-Research : ZOR ; mathematical methods of operations research
    Publisher: Heidelberg :Physica-Verl.,
    Year of publication: 1972-1995
    Dates of Publication: 16.1972 - 42.1995
    ISSN: 0340-9422
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Ablauf- und Planungsforschung
    Subsequent Title: Forts. ---〉:Mathematical methods of operations research
    Note: Ser. A, Theorie = H. 1,3,5,7 d. Jg.; Ser. B, Praxis = H. 2,4,6,8 d. Jg. , Deutsche Gesellschaft für Operations-Research
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  • 23
    Journal/Serial
    Journal/Serial
    New York, NY :ACM, ; 2.1971/72 - 16.1985; 19.1988 - 26.1995; damit Ersch. eingest.
    Title: SIGMICRO newsletter : a quarterly publ. of the Special Interest Group on Microprogramming
    Author: Association for Computing Machinery / Special Interest Group on Microprogramming
    Publisher: New York, NY :ACM,
    Year of publication: 1971-1995
    Dates of Publication: 2.1971/72 - 16.1985; 19.1988 - 26.1995; damit Ersch. eingest.
    ISSN: 0163-5751 , 1050-916X
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Association for Computing Machinery / Special Interest Committee on Microprocessing: SICMICRO newsletter
    Subsequent Title: 17.1986 - 18.1987 ---〉:Association for Computing Machinery / Special Interest Group on Microprogramming: SIGMICRO TCMICRO newsletter
    Additional Information: Beil. ---〉:Microprogramming bibliography
    Additional Information: 9,4=11; 12,4=14; 13,4=15 von:Micro
    Additional Information: 20,3=22 von:International Workshop on Microprogramming and Microarchitecture: Annual International Workshop on Microprogramming and Microarchitecture
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  • 24
    Title: Data-base 〈New York,NY〉 : db ; a quarterly publication of the Special Interest Group on Business Information Technology of the Association for Computing Machinery
    Contributer: Association for Computing Machinery / Special Interest Group on Business Data Processing , Association for Computing Machinery / Special Interest Group on Business Information Technology
    Publisher: New York, NY,
    Year of publication: 1971-1994
    Dates of Publication: 3.1971 - 25.1994
    ISSN: 0095-0033
    Type of Medium: Book
    Former Title: Vorg. ---〉 SIGBDP news-letter
    Subsequent Title: Forts. ---〉:¬The¬ data-base for advances in information systems
    Additional Information: Einzelne Bd. zugl. Bd. von:Association for Computing Machinery / Special Interest Group on Management of Data: SIGMOD record
    Additional Information: 12,4u.13,1=2 von:Data-base directions
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  • 25
    Journal/Serial
    Journal/Serial
    München :Franzis-Verl., ; 1981 - 1994,6
    Title: MC 〈München〉 : Computerpraxis für technische Anwender
    Publisher: München :Franzis-Verl.,
    Year of publication: 1981-1994
    Dates of Publication: 1981 - 1994,6
    ISSN: 0720-4442 , 0941-777X , 0943-5409
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Aufgeg. in ---〉:DOS international
    Note: Auch mit fehlerhafter Jg.-Zählung im Impressum
    Additional Information: 1992 Sonderh. ---〉:WINbox
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  • 26
    Journal/Serial
    Journal/Serial
    London [u.a.], ; 1.1969 - 39.1993
    Title: International journal of man machine studies
    Publisher: London [u.a.],
    Year of publication: 1969-1993
    Dates of Publication: 1.1969 - 39.1993
    ISSN: 0020-7373
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:International journal of human - computer studies
    Note: Index 1/4.1969/72 in: 4.1972
    Additional Information: 10,3=5 von:Man Computer Communications Conference: Proceedings
    Parallel Title: Internetausg. ---〉:International journal of man machine studies
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  • 27
    Title: SIGSMALL - PC notes : a publication of the Special Interest Group on Small and Personal Computing Systems and Applications, Association for Computing Machinery
    Author: Association for Computing Machinery / Special Interest Group on Small and Personal Computing Systems and Applications
    Publisher: New York, NY :ACM,
    Year of publication: 1984-1993
    Dates of Publication: 10.1984,4 - 19.1993/94,2(1993)
    ISSN: 0893-2875
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Association for Computing Machinery / Special Interest Group on Small Computing Systems and Applications: SIGSMALL newsletter
    Subsequent Title: Forts. ---〉:Association for Computing Machinery / Special Interest Group on Individual Computing Environments: SIGICE bulletin
    Note: Zählung von "SIGSMALL newsletter" übernommen
    Parallel Title: Internetausg. ---〉:Association for Computing Machinery / Special Interest Group on Small and Personal Computing Systems and Applications: ACM SIGSMALL - PC notes
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  • 28
    Journal/Serial
    Journal/Serial
    Duluth, Minn. [u.a.], ; 1.1989 - 5.1993; damit Ersch. eingest.
    Title: Impact of computing in science and engineering
    Publisher: Duluth, Minn. [u.a.],
    Year of publication: 1989-1993
    Dates of Publication: 1.1989 - 5.1993; damit Ersch. eingest.
    ISSN: 0899-8248
    Type of Medium: Journal/Serial
    Language: Undetermined
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  • 29
    Journal/Serial
    Journal/Serial
    München :Oldenbourg, ; 28.1986 - 34.1992
    Title: Informationstechnik : it ; Computer, Systeme, Anwendungen
    Publisher: München :Oldenbourg,
    Year of publication: 1986-1992
    Dates of Publication: 28.1986 - 34.1992
    ISSN: 0179-9738 , 0013-5720
    Type of Medium: Journal/Serial
    Language: Undetermined
    Former Title: Vorg. ---〉:Elektronische Rechenanlagen
    Subsequent Title: Forts. ---〉:Informationstechnik und technische Informatik
    Note: it-Seminar
    Additional Information: Beil. ---〉:Euro-KI-Führer
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  • 30
    Title: SIGACT news : publ. by the ACM Special Interest Group on Automata and Computability Theory
    Author: Association for Computing Machinery / Special Interest Group on Automata and Computability Theory
    Contributer: Association for Computing Machinery / Special Interest Committee on Automata and Computability Theory
    Publisher: New York, NY :ACM,
    Year of publication: 1969-1992
    Dates of Publication: 1.1969 - 23.1992,2 = Nr. 1-83
    ISSN: 0163-5700
    Type of Medium: Journal/Serial
    Subsequent Title: Forts. ---〉:Association for Computing Machinery / Special Interest Group on Algorithms and Computation Theory: SIGACT news
    Additional Information: In 12.1980,2 Index 1/12.1969/80 von ---〉:Symposium on Theory of Computing: Conference record of the ... annual ACM Symposium on Theory of Computing
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  • 31
    Journal/Serial
    Journal/Serial
    Utrecht :VNU Science Press, ; 1.1986 - 6.1991
    Title: Soviet journal of numerical analysis and mathematical modelling
    Publisher: Utrecht :VNU Science Press,
    Year of publication: 1986-1991
    Dates of Publication: 1.1986 - 6.1991
    ISSN: 0169-2895
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: Forts. ---〉:Russian journal of numerical analysis and mathematical modelling
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  • 32
    Title: SIGPLAN notices : a monthly publication of the Special Interest Group on Programming Languages of the Association for Computing Machinery
    Author: Association for Computing Machinery / Special Interest Group on Programming Languages
    Publisher: New York, NY :ACM,
    Year of publication: 1966-1991
    Dates of Publication: 1.1966 - 26.1991,9u.11
    ISSN: 0362-1340
    Type of Medium: Journal/Serial
    Language: Undetermined
    Subsequent Title: 26.1991,10 u. Forts. ---〉:Association for Computing Machinery / Special Interest Group on Programming Languages: ACM SIGPLAN notices
    Additional Information: 6,2=1971 von:Symposium on Data Structures in Programming Languages: Proceedings of a Symposium on Data Structures in Programming Languages
    Additional Information: 17,4=10,2; 22,10=15,5; 24,spec.iss.=17,2; 26,4=19,2 von:Computer architecture news
    Additional Information: 21,10=1986 von:Workshop on Object Oriented Programming: Transcript
    Additional Information: 11,6=10,1 von:Computer graphics
    Additional Information: 16,6=2,1/2 von:Association for Computing Machinery / Special Interest Group on Office Automation: SIGOA newsletter
    Additional Information: 14,8=1979; 17,6=1982; 19,6=1984; 21,7=1986 von:Symposium on Compiler Construction: Proceedings of the SIGPLAN Symposium on Compiler Construction
    Additional Information: 20,7=1985 von:Symposium on Language Issues in Programming Environments: Proceedings of the ACM SIGPLAN ... Symposium on Language Issues in Programming Environments
    Additional Information: 19,5=1; 22,1=2; 24,2=3 von:Software Engineering Symposium on Practical Software Development Environments: Proceedings of the ACM SIGSOFT SIGPLAN Software Engineering Symposium on Practical Software Development Environments
    Additional Information: 22,10=2; 24,spec.iss.=3 von:International Conference on Architectural Support for Programming Languages and Operating Systems: Proceedings
    Additional Information: 23,7=1988; 24,7=1989; 25,6=1990 von:Conference on Programming Language Design and Implementation: Proceedings of the SIGPLAN ... Conference on Programming Language Design and Implementation
    Additional Information: 21,11=1; 22,12=2; 23,11=3; 24,10=4 von:OOPSLA: Conference proceedings
    Additional Information: 22,10=21,4; 24,spec.iss.=23,spec.iss.; 26,4=25,spec.iss. von:Operating systems review
    Additional Information: 17,4=1982 von:Symposium on Architectural Support for Programming Languages and Operating Systems: Proceedings
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  • 33
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Several mutations in mice produce complex patterns of neuronal degeneration of the cerebellum and of its afferent pathways. In the staggerer (sg/sg) mutant, atrophy of the lymphoid organs and immunological abnormalities have been described. To search for a possible link between the neurological and the immune disorders in this mutant, we studied the production by its peripheral macrophages of interleukin-1 (IL-1), which roles in both immune and nervous systems are well established. Suspensions of peritoneal and/ or spleen macrophages from mutants and their appropriate controls were stimulated in vitro by lipopolysaccharide. Northern and dot blots, performed with murine IL-1 cDNA probes, revealed a clear-cut hyperexpression of IL-1 mRNA in staggerer macrophages. An IL-1 bioassay using the IL-1-responsive D10.G4 cell line also revealed a sixfold increase of IL-1 activity in the macrophage supernatants of staggerer mutant mice. The hyperproduction was found in 3-week to 1-year-old staggerer and also in heterozygous (+/sg) mice. A similar phenomenon existed in cerebellar mutants lurcher, Purkinje cell degeneration (pcd), and to a lesser extent reeler and wobbler, but was absent in the neurological mutants weaver, jimpy, and motor end plate disease (medH). These observations establish that in several point mutations in mice, central nervous degeneration is associated with dysregulation of IL-1 production by peripheral macrophages.
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  • 34
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Recent studies have demonstrated that several transcription factor genes are rapidly activated by neuronal stimulation. For example, we have found that prolonged and repeated seizure activity produced by administration of chemical convulsants induces a rapid and transient increase in mRNA levels of four immediate early genes in rat brain. These genes, zif/268, c-fos, c-jun, andjun-B, encode sequence specific DNA binding proteins thought to act as transcription regulatory factors. To ascertain whether a brief electrically induced seizure discharge of the type utilized in clinical electroconvulsive treatment is sufficient to induce a similar genomic response, we have examined the response of these mRNAs in rat brain following single and repeated electroshock-induced seizures. After electroshock, mRNA levels of each of these genes increase within 15 min, and all except cjun return to near baseline levels within 4 h. Although this response is most prominent in granule cell neurons of the hippocampus, increases are also apparent in neocortex and pyriform cortex. The rapid mRNA response persists in animals receiving a chronic electroshock protocol similar to that used in clinical electroconvulsive therapy. Intrahippocampal infusion of the sodium channel antagonist tetrodotoxin blocks hippocampal mRNA responses without blocking seizures, indicating a role for electrical excitation in the electroshockinduced mRNA response. By contrast, pretreatment with anticonvulsants or selective NMDA antagonists, which reduce seizure intensity and block hindlimb extension, fails to alter mRNA responses, suggesting that seizure induction, rather than spread, is linked to these mRNA responses. Because electroshock induces robust, highly reproducible mRNA responses, it may be useful to study the neuronal genomic response to stimulation.
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  • 35
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Ganglioside analysis of human motor and sensory nerves revealed that ceramide compositions of sensory nerve GD1a, GD1b, and GMl differed apparently from those in the motor nerve. These gangliosides from sensory nerve contained a large amount of long-chain fatty acids and d18:1 as a major long chain base. On the contrary, the motor nerve gangliosides contained C16–18 fatty acids and a large amount of d20:1 besides d 18:1. Furthermore, these gangliosides were enriched more in the axon fraction than in the myelin fraction. LM1, which was a major ganglioside in myelin from human peripheral nerve, was composed of similar ceramide compositions in the two nerves. The present findings suggest that the characteristic ceramide species of nerve gangliosides may reflect in part properties of their own neurons.
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  • 36
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The monoclonal L5 antibody reacts with an N-glycosidically linked carbohydrate structure which is present on the neural cell adhesion molecule L1, neural chondroitin sulfate proteoglycans, and other not yet identified glycosylated proteins. Using this antibody, we isolated and characterized proteoglycans from adult mouse brain and cultured astrocytes biosynthetically labeled with Na235SO4 and a 3H-amino acid mixture. Our data suggest that the L5 proteoglycans of both sources are identical in their biochemical properties. The apparent molecular mass of the L5 proteoglycan is approximately 500 kDa. Digestion of the iodinated L5 proteoglycan from mouse brain and of the [35S]methionine-labeled L5 proteoglycan from cultured astrocytes with proteinase-free chondroitinases ABC and AC revealed three major core proteins with apparent molecular masses of approximately 380, 360, and 260 kDa. These represent molecularly distinct protein cores.
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  • 37
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of chronic versus acute administration of lithium on receptor-linked phosphoinositide metabolism was assessed by comparing the change in the cerebral cortex levels of myo-inositol 1-phosphate in response to pilocarpine, physostigmine, or pargyline in rats. Rats were exposed to either 29 consecutive days of LiCl injections or 27 and 39 days of dietary Li2CO3, followed by injected LiCl at the end of the diet to insure a constant level of exposure to the drug. In each experiment, an acute group received a single injection of LiCl 20–24 h before they were killed. One hour before being killed, some of the animals acutely exposed to lithium and some of the animals chronically exposed to lithium each received pilocarpine, physostigmine, or pargyline. At the conclusion of the experiment, the rats were killed and brain levels of myo-inositol 1-phosphate and lithium were determined. A differential production of myo-inositol 1-phosphate in groups receiving acute versus chronic lithium would provide evidence of a change in receptor-linked phosphoinositide metabolism due to the chronic administration of lithium. Brain levels of mvo-inositol 1-phosphate are dependent on tissue lithium concentrations; consequently, significant differences observed in brain lithium levels between the groups receiving acute versus chronic lithium prevented a meaningful assessment of the effect of the mode of lithium administration on the production of myo-inositol 1-phosphate in those groups. Stepwise multiple regression analysis and the measured brain lithium levels were used to assess the response of myo-inositol 1-phosphate levels to stimulation in animals receiving acute or chronic lithium treatment. The results of the analysis indicate that there would have been no differences in the response to drugs when comparing the two routes of lithium administration if the lithium levels had been identical in both the acute and chronic lithium groups. These results also suggest that multiple regression analysis can be used with an established data base to aid in the interpretation of the results of experiments in which changes in brain myo-inositol 1-phosphate levels are used as an index of phosphoinositide metabolism. The possibility is discussed that the effects of lithium on phosphoinositide signalling are already present in the group receiving a single acute dose of LiCl and that this effect persists over the course of chronic administration.
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  • 38
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Monoclonal antibody HNK-1-reactive carbohydrate epitope is expressed on proteins, proteoglycans, and sulfoglucuronyl glycolipids (SGGLs). The developmental expression of these HNK-1-reactive antigens was studied in rat cerebellum. The expression of sulfoglucuronyl lacto-N-neotetraosylceramide (SGGL-1) was biphasic with an initial maximum at postnatal day one (PD 1), followed by a second rise in the level at PD 20. The level of sulfoglucuronyl lacto-N-norhexaosyl ceramide (SGGL-2) in cerebellum was low until PD 15 and then increased to a plateau at PD 20. The levels of SGGLs increased during postnatal development of the cerebellum, contrary to their diminishing expression in the cerebral cortex. The expression of HNK-1-reactive glycoproteins decreased with development of the rat cerebellum from PD 1. Several HNK-1-reactive glycoproteins with apparent molecular masses between 150 and 325 kDa were visualized between PD 1 and PD 10. However, beyond PD 10, only two HNK-1-reactive bands at 160 and 180 kDa remained. The latter appeared to be neural cell adhesion molecule, N-CAM-180. A diffuse HNK-1-reactive band seen at the top of polyacrylamide electrophoretic gels was due mostly to proteoglycans. This band increased in its reactivity to HNK-1 between PD 15 and PD 25 and then decreased in the adult cerebellum. The lipid antigens were shown by two complementary methodologies to be localized primarily in the molecular layer and deep cerebellar nuclei as opposed to the granular layer and white matter. A fixation procedure which eliminates HNK-1-reactive epitope on glycoproteins and proteoglycans, but does not affect glycolipids, allowed selective immunoreactivity in the molecular layer and deep cerebellar nuclei. In order to confirm this localization, SGGLs were analyzed by HPTLC-immunoverlay method in micro-dissected cerebellar layers from freeze-dried cryocut sections: they were found primarily in the molecular layer and deep cerebellar nuclei and were undetectable in the granule cell layer and white matter. These results, along with the lack of SGGLs and disialosyl lacto-N-neotetraosylceramide (LD1) in several Purkinje cell-deficient murine mutants reported previously, indicate that these glycolipids are associated specifically with Purkinje cell dendrites in the molecular layer and Purkinje cell axon synapses in deep cerebellar nuclei.
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  • 39
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The aim of the present investigation was to study and compare the in vitro binding properties of the two ra-dioligands N-[3H]methylspiperone ([3H]NMSP) and [3H]raclopride. These compounds, labeled with 11C, have been extensively used in positron emission tomography studies on central dopamine D2 receptors in schizophrenic patients, although with diverging results. One study (using [11C]NMSP) showed an increased dopamine receptor density in drug-naive schizophrenic patients, whereas in another study (using [11C]raclopride) the density in schizophrenic patients was no different from that in healthy controls. In the present study, using in vitro binding techniques, the density of the binding sites was found to be similar irrespective of which of the two radioligands was used (20 fmol/mg wet weight in rat striatum and 10 fmol/mg in human putamen; the 5-hydroxytryptamine2 receptors were blocked with 40 nM ketanserin). [3H]NMSP had a 10-fold higher affinity (KD, 0.3 nM in rat striatum and 0.2 nM in human putamen) than [3H]raclopride (KD, 2.1 nM in rat striatum and 3.9 nM in human putamen), which was consistent with the longer dissociation half-life of [3H]NMSP compared with [3H]raclopride (14.8 and 1.19 min, respectively). There was an approximate overall similarity between the inhibition constants for five dopamine antagonists, chlorpromazine, haloperidol, raclopride, remoxipride, and NMSP, when using either radioligand. The K1 values were, however, two- to fourfold higher when using [3H]NMSP as the radioligand, irrespective of inhibiting compound, except for chlorpromazine (and haloperidol in human putamen). NMSP was found to inhibit the binding of [3H]raclopride competitively, whereas raclopride inhibited the binding of [3H]NMSP both competitively and noncompetitively. This difference suggests that part of the binding site is exclusively used by NMSP and can only be allosterically interfered with by raclopride. It is proposed that [3H]NMSP binds to an additional set of accessory binding sites, presumably located more distantly from the agonist binding active site than the sites to which [3H]raclopride binds.
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  • 40
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Poly-α-2,8-N-acetylneuraminic acid (poly-α-2,8-NeuAc) is developmentally expressed in neural tissue of higher animals, where it is covalently attached to the neural cell adhesion molecule (NCAM), a large integral membrane glycoprotein mediating cell-cell adhesion during neuronal development. NCAM exists in several molecular forms, of which only embryonic NCAM carries lengthy chains (n 〉 5) of poly-α-2,8-NeuAc. Chemically identical poly-α-2,8-NeuAc of bacterial origin is an important virulence factor in infections caused by Neisseria meningitidis group B and Escherichia coli K1, the predominant pathogens of bacterial meningitis. A quantitative enzyme-linked immunoassay was developed using monoclonal antibody (MAb) 735, an MAb specifically recognizing poly-α-2,8-NeuAc, and applied to CSF specimens from younger children. Poly-α-2,8-NeuAc contents were within the range of 20-0.2 μg/ml, decreasing from day 1 to day 300. Immunoprecipitation, immunoblot with a rabbit anti-mouse NCAM serum recognizing the protein part of human NCAM by cross-reactivity, affinity enrichment using immobilized MAb 735, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that poly-α-2,8-NeuAc in CSF is bound to human NCAM, probably NCAM-120.
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  • 41
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: To identify the involvement of dopamine receptors in the transmembrane signaling of the adenosine receptor-G protein-adenylate cyclase system in the CNS, we examined the effects of pertussis toxin (islet-activating protein, IAP) and apomorphine on A1 adenosine agonist (-)N6-R-[3H]phenylisopropyladenosine ([3H]PIA) and antagonist [3H]xanthine amine congener ([3H]XAC) binding activity and adenylate cyclase activity in cerebral cortex membranes of the rat brain. Specific binding to a single class of sites for [3H]XAC with a dissociation constant (KD) of 6.0 ± 1.3 nM was observed. The number of maximal binding sites (Bmax) was 1.21 ± 0.13 pmol/mg protein. Studies of the inhibition of [3H]XAC binding by PIA revealed the presence of two classes of PIA binding states, a high-affinity state (KD= 2.30 ±1.16 nM) and a low-affinity state (KD= 1,220 ± 230 nM). Guanosine 5′-(3-O-thio)triphosphate or IAP treatment reduced the number of the high-affinity state binding sites without altering the KD for PIA. Apomorphine (100 μM) increased the KD value 10-fold and decreased Bmax by ∼20% for [3H]PIA. The effect of apomorphine on the KD value increase was irreversible and due to a conversion from high-affinity to low-affinity states for PIA. The effect was dose dependent and was mediated via D2 dopamine receptors, since the D2 antagonist sulpiride blocked the phenomenon. The inhibitory effect of PIA on adenylate cyclase activity was abolished by apomorphine treatment. There was no effect of apomorphine on displacement of [3H]quinuclidinyl benzilate (muscarinic ligand) binding by carbachol. These data suggest that A1 adenosine receptor binding and function are selectively modified by D2 dopaminergic agents.
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  • 42
    Electronic Resource
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Synaptosomes from rat forebrain can easily be isolated by combining centrifugation with partition in an aqueous two-phase system composed of dextran T500 and polyethylene glycol 4000 in which synaptosomes have an extreme affinity for the upper phase. The fraction thus obtained has been characterized by electron microscopy and biochemical markers for synaptosomes and some other cell components. The contamination by microsomes, free mitochondria, and myelin was 4.4, 3.2, and 0.1%, respectively. The morphometric analysis of the electron micrographs shows that 〉60% of the structures are synaptosomes. This preparation of the isolation procedure is remarkably short (〈1 h), formance as assayed by their respiratory activities and ATP level in the absence and presence of depolarizing agents. Synaptosomes prepared by phase partition release the neurotransmitter glutamate in a Ca2+-dependent manner. The duration of the isolation procedure is remarkably short (〈1 h), no ultracentrifuge is required, and the method can be applied for small- or large-scale preparations.
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  • 43
    Electronic Resource
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Incubation of various authentic peptides with rat CSF in vitro and analysis of their products by HPLC demonstrated the presence in CSF of a peptidyl dipeptidase [peptidyl dipeptide hydrolase; angiotensin I converting enzyme (ACE); kininase II; EC 3.4.15.1] which sequentially degraded bradykinin (BK) by liberating the carboxy-terminal dipeptides and converted angiotensin I to angiotensin II. This CSF enzyme was gel-chromatographed by means of HPLC., and the molecular weight was estimated. The susceptibility to various peptidase inhibitors of the rat CSF enzyme, as well as the effect of NaC1 on the degradation of BK and Hip-His-Leu catalyzed by it, was also determined. These properties were compared with those of ACE or kininase II from brain or other tissues, as described in the literature. NaC1 was shown to exert specific and concentration-dependent effects on each step of the sequential degradation of BK, via BK(1–7) to BK(l–5), catalyzed by the enzyme. In addition, the enzyme system for metabolism of BK appears to differ between rat CSF and blood, the former containing exclusively kininase II, whereas the latter contains both kininase I (carboxypeptidase N; EC 3.4.12.7) and kininase II.
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  • 44
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The production of 14CO2 and [14C]acetylcholine from [U-14C]glucose was determined in vitro using tissue prisms prepared from the dorsolateral striatum (a region developing extensive neuronal loss following ischemia) and the paramedian neocortex (an ischemia-resistant region) following 30 min of forebrain ischemia and recirculation up to 24 h. Measurements were determined under basal conditions (5 mMK+) and following K+ depolarization (31 mM K+). The production of 14CO2 by the dorsolateral striatum was significantly reduced following 30 min of ischemia for measurements in either 5 or 31 mM K+ but recovered toward preischemic control values during the first hour of recirculation. Further recirculation resulted in 14CO2 production again being reduced relative to control values but with larger differences (20–27% reductions) detectable under depolarized conditions at recirculation times up to 6 h. Samples from the paramedian neocortex showed no significant changes from control values at all time points examined. [14C]Acetylcholine synthesis, a marker of cholinergic terminals that is sensitive to changes in glucose metabolism in these structures, was again significantly reduced only in the dorsolateral striatum. However, even in this tissue, only small (nonstatistically significant) differences were seen during the first 6 h of recirculation, a finding suggesting that changes in glucose oxidation during this period were not uniform within all tissue components. The results of this study provide evidence that in a region susceptible to ischemic damage there were specific changes during early recirculation in the metabolic response to depolarization. This apparent inability to respond appropriately to an increased need for energy production could contribute to the further deterioration of cell function in vivo and ultimately to the death of some cells.
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  • 45
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The subcellular and regional distribution of endooligopeptidase (EC 3.4.22.19), an enzyme capable of generating enkephalin by single cleavage from enkephalin-containing peptides, was determined by an enzymatic assay using metorphamide and by immunochemical techniques in the CNS of the rat. The rat CNS contains a membrane-associated form of endo-oligopeptidase, an enzyme predominantly associated with the soluble fraction of brain homogenates. Sub-cellular fractionation showed that ∼17% of the total activity of the enzyme is associated with membrane fractions including synaptosomes. Synaptosomal membranes were prepared from neocortex, striatum, hypothalamus, medulla, spinal cord, and cerebellum. The amount of EC 3.4.22.19 activity solubilized by 3-([3-cholamidopropyl]dimethylammonio)-1-propanesulfonate from synaptosomal membranes was similar in neocortex, striatum, and hypothalamus, being three- to 10-fold greater than in spinal cord, cerebellum, and medulla. A polyclonal antibody exhibiting high affinity for endo-oligopeptidase was raised in rabbits against the purified rat brain enzyme and used to localize endo-oligopeptidase by Western blotting and by immunoperoxidase techniques. A strong band corresponding to the Mr of EC 3.4.22.19 was found in solubilized proteins obtained from synaptosomal membranes prepared from hypothalamus, neocortex, and striatum when subjected to Western blotting. The immunohistochemical localization of endo-oligopeptidase indicated that the immunoreactivity was confined to gray matter in regions known to be rich in peptide-containing neurons such as the striatum. In the cerebellum, a region poor in peptides, no staining could be detected. The nonuniform distribution of endo-oligopeptidase in rat brain suggests a role in neurotransmitter processing in the CNS.
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  • 46
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of inhibitors of protein synthesis (actinomycin D, cycloheximide), proteases (leupeptin), and intracellular transport (colchicine, monensin) on the γ-aminobutyric acid (GABA) agonist [4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP)]-induced changes in morphological differentiation and GABA receptor expression was investigated in cultured cerebellar granule cells. After 4 days in culture the neurons were exposed to the inhibitors for 6 h in the simultaneous presence of THIP. Subsequently, cultures were either fixed for electron microscopic examination or used for preparation of membranes for [3H]GABA binding assays. In some experiments the functional activity of the newly induced low-affinity GABA receptors was assessed by investigation of the ability of GABA to inhibit neurotransmitter release from the neurons. These experiments were performed to differentiate between an intracellular and a plasma membrane localization of the receptors. In all experiments cultures treated with THIP alone served as controls. The inhibitors of protein synthesis totally abolished the ability of THIP to induce low-affinity GABA receptors. In contrast, the inhibitors of intracellular transport as well as the protease inhibitor did not affect this parameter. However, studies of effects of GABA on transmitter release from monensintreated cultures showed that transmitter release could not be inhibited by GABA in these cells in spite of the presence of low-affinity GABA receptors in the membrane preparations. This indicates that the low-affinity receptors were not located in the plasma membrane. This is in good agreement with the corresponding morphological findings, that monensin treatment led to an intense vacuolization of the Golgi apparatus, thereby preventing intracellular transport of the newly synthesized GABA receptors. No qualitative alteration of the general ultrastructure was observed in cells cultured in the simultaneous presence of THIP and actinomycin, cycloheximide. or colchicine. However, these inhibitors reduced the cytoplasmic density of the different organelles involved in the cellular machinery for synthesis and intracellular transport compared to cells grown in the presence of THIP alone. These results suggest that the THIP-induced alterations in the GABA receptor expression in cerebellar granule cells requires de novo synthesis of low-affinity GABA receptors, which in turn is dependent on proper function of the organelles involved in synthesis and intracellular transport of proteins destined for insertion into the plasma membrane.
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  • 47
    Electronic Resource
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Transferrin receptors were characterized with 125Iferrotransferrin on membrane fractions prepared from the rodent forebrain. The distribution of transferrin receptors in the rat brain was investigated further by in vitro autoradiography. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 2 nM and a binding site density of 15 pmol/g. The Hill coefficient derived from these data was 1.05. indicating the absence of cooperativity and that 125I-ferrotransferrin binds to a single class of sites. Estimates of the kinetically determined Kd for forebrain membranes were within the 2–4 nM range, in agreement with the equilibrium measurements. Apotransferrin and ferrotransferrin competitively displaced the binding of 125I-ferrotransferrin, while ferritin, albumin, and cytochrome c failed to compete for the binding site. Ceruloplasmin, the copper transport protein, was a weak inhibitor of 125I-ferrotransferrin binding. Autoradiographic localization studies demonstrate a heterogeneous distribution of transferrin receptors in the rat brain. Transferrin receptor densities were markedly elevated over the cerebral cortex and the hippocampus. Moderate to high 125I-ferrotransferrin binding was also apparent throughout areas involved in motor functions, including the caudate-putamen, the nucleus accumbens, the substantia nigra, the red nucleus, and the cerebellum.
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  • 48
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In synaptosomal brain membranes, the addition of oleic acid (cis), elaidic acid (trans), and the cis and trans isomers of vaccenic acid, at a concentration of 0.87 μmol of lipid/mg of protein, strongly reduced the Bmax and, to a lesser degree, the binding affinity of the μ-selective opioid [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAMGO). At comparable membrane content, the cis isomers of the fatty acids were more potent than their trans counterparts in inhibiting ligand binding and in decreasing membrane microviscosity, both at the membrane surface and in the core. However, trans-vaccenic acid affected opioid receptor binding in spite of just marginally altering membrane microviscosity. If the receptors were uncoupled from guanine nucleotide regulatory protein, an altered inhibition profile was obtained: the impairment of KD by the fatty acids was enhanced and that of Bmax reduced. Receptor interaction of the δ-opioid [3H](D-Pen2,D-Pen5)enkephalin was modulated by lipids to a greater extent than that of [3H]DAMGO: saturable binding was abolished by both oleic and elaidic acids. The binding of [3H]naltrexone was less susceptible to inhibition by the fatty acids, particularly in the presence of sodium. In the absence of this cation, however, cis-vaccenic acid abolished the low-affinity binding component of [3H]naltrexone. These findings support the membrane model of opioid receptor sequestration depicting different ionic environments for the μ- and δ-binding sites. The results of this work show distinct modulation of different types and molecular states of opioid receptor by fatty acids through mechanisms involving membrane fluidity and specific interactions with membrane constituents.
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  • 49
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzodiazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained ∼ 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased ∼ 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.
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  • 50
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A new acidic protein specifically present in the brain was purified to homogeneity from bovine brain. The apparent molecular mass was estimated to be 14 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 57 kDa by gel filtration, a finding suggesting that it exists as a tetramer under physiological conditions. The protein had a high content of Glu and Pro, and its pI was 4.3. The first six amino acid residues of the protein were Met-Asp-Val-Phe-Met-Lys, and the amino terminal was blocked. The distribution of the protein examined by Ouchterlony gel immunodiffusion indicates that it is present specifically in brain, including rat, human, and bovine, but could not be detected in 10 other rat tissues examined. The protein was absent in Purkinje cell bodies, as examined by electron microscopic immunocyto-chemistry, but was present in nerve terminals that make synapse-like contacts with Purkinje cells and in neurons with dark granules in the globus pallidus of the rat.
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  • 51
    Electronic Resource
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of tetanus toxin on neuropeptide hormone release from isolated nerve endings of the neural lobe of rat pituitaries (neurosecretosomes) was measured in a perfusion system. Tetanus toxin inhibited depolarization-evoked release of oxytocin and vasopressin in a time- and dose-dependent manner. At 1 μg/ml, tetanus toxin blocked stimulated release by 85%. Tetanus toxin that was preincubated with a neutralizing monoclonal antibody or heated to 100°C had no effect on hormone release. The ionophores A23187 and ionomycin were potent stimulators of hormone release in control nerve endings, but were not able to overcome the effect of tetanus toxin in intoxicated nerve endings. 8-Bromo cyclic GMP. which has been reported to reverse the action of tetanus toxin in PC12 cells, had no effect on the action of tetanus toxin in neurosecretosomes. Neurosecretosomes are the first system in which tetanus toxin has been shown to block release from peptidergic nerve terminals. They appear to be a valuable in vitro system for studying the biochemical mechanism of tetanus toxin action.
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  • 52
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In a developmental study, we have shown that DM-20 is present before proteolipid protein (PLP) in the fetal bovine cerebral hemispheres. When the white matter appears (27–30 weeks of gestation), the amount of DM-20 drastically increases. DM-20 remains the major proteolipid until birth. PLP is detected only 2–4 weeks after the appearance of white matter, that is, more than 4 weeks after the appearance of DM-20. The early appearance of DM-20 at the beginning of myelination raises the question of its particular function. In the adult bovine cerebral hemispheres, PLP is the major proteolipid but DM-20 remains quantitatively important because the PLP/DM-20 ratio ranges from 1.5 to 1.7. In the same developmental study we have, in the fetal cerebral hemispheres, isolated and characterized a novel proteolipid (apparent Mr 20,000), which appears even before DM-20 and is not detected in the adult brain. It is structurally related to PLP and DM-20 because the first 31 N-terminal amino acid residues are the same. However, in immunoblot. it did not react either with the antitridecapeptide 117–129 antiserum of PLP or with the anti-C-terminal hexapeptide antiserum of PLP.
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  • 53
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A number of studies have found that the chronic administration of nicotine causes an increase in the density of nicotinic binding sites in the brain, but it is not known whether these additional binding sites are functionally active receptors. In this study, the effects of 1-week administration of the potent nicotinic agonist, (+)-anatoxin-a (96 nmol/day via osmotic minipumps), was assessed on [3H]nicotine binding and [3H]dopamine uptake and release in rat striatal synaptosomes. Chronic (+)-anatoxin-a treatment resulted in a 32% increase in the Bmax of [3H]nicotine binding in anatoxin-treated animals compared to control. There was a 43% increase in the activity of 3 μM nicotine to release [3H]dopamine from synaptosomes of anatoxin-treated animals, but the release induced by 20 mM K+ depolarization was unaffected. There was no effect of chronic (+)-anatoxin-a treatment on the uptake of [3H]dopamine. A strong positive correlation (r= 0.64) was found between the density of [3H]nicotine binding sites and the nicotine-induced stimulation of [3H]dopamine release in individual animals. These results indicate that (+)-anatoxin-a, like nicotine, produces an up-regulation of nicotine binding sites following chronic administration, and that these additional sites are functional receptors capable of mediating the release of dopamine from striatal synaptosomes.
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  • 54
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of the general anesthetic propofol on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to unwashed membrane preparations from rat cerebral cortex was studied and compared to that of other general anesthetics (pentobarbital, alphaxalone) which are known to enhance GABAergic transmission. Propofol produced a concentration-dependent complete inhibition of [35S]TBPS binding, an effect similar to that induced by pentobarbital and alphaxalone, although these agents differ markedly in potency (alphaxalone 〉 propofol 〉 pentobarbital). The concomitant addition of propofol either with alphaxalone or pentobarbital produced an additive inhibition of [35S]TBPS binding, suggesting separate sites of action or different mechanisms of these drugs. Moreover, although bicuculline (0.1 μM) completely antagonized the propofol-induced inhibition of [35S]TBPS binding, the effect of this anesthetic was not due to a direct interaction with the γ-aminobutyric acidA (GABAA) recognition site. In fact, propofol, like alphaxalone and pentobarbital, markedly enhanced [3H]GABA binding in the rat cerebral cortex. Finally, propofol was able to enhance [3H]GABA binding in membranes previously incubated with the specific chloride channel blocker picrotoxin. Taken together these data strongly suggest that propofol, like other anesthetics and positive modulators of GABAergic transmission, might exert its pharmacological effects by enhancing the function of the GABA-activated chloride channel.
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  • 55
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Amplification of rat intestine mRNAs was performed by the reverse transcriptase-polymerase chain reaction (RT-PCR) using various oligonucleotide primers mainly corresponding to the translated region of the enkephalinase (EC 3.4.24.11, membrane metalloendopeptidase, MME 1) gene. In addition to the expected transcript, a shorter one was identified and its sequence indicated that it corresponds to an alternatively spliced mRNA from which exons 5–18 of MME I are deleted. It encodes a deduced 255 amino acid protein, MME II, instead of the 742 amino acid sequence of enkephalinase. The deduced structure of MME II is consistent with its being a membrane-bound, zinc-containing glycoprotein with a modified peptidase activity. MME II mRNA is also expressed, together with MME I mRNA, in brain and thyroid in a tissue-specific manner.
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  • 56
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 57
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 3-Bromopyruvate inhibits pyruvate decarboxylase in brain homogenates and causes a 90% drop in acetylcholine tissue content at a concentration of 2 mM. Stereotaxic injection of 3-bromopyruvate into the basal forebrain causes after 7 days a 40% drop of acetylcholine concentration and pyruvate decarboxylase activity in the cortex and hippocampus, and greater decreases at the site of injection. However, values return to normal 18 days after injection. Choline ace-tyltransferase is partially inhibited only at the site of injection after 7 days. Choline transport and choline concentration are not affected at either 7 or 18 days after injection. Impairments in spontaneous alternation and in retention of passive avoidance were seen only 7 days after the injection. The results suggest that stereotaxic injection of bromopyruvate can induce discrete reversible cholinergic lesions on a time scale useful for behavioural experiments and for comparison with neurodegeneration.
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  • 58
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We have studied the effect of a dietary deprivation of n-3 fatty acids on the activity of the dopamine (DA)-de-pendent adenylate cyclase in the rat retina. Experiments were conducted in 6-month-old rats raised on semipurified diets containing either safflower oil (n-3 deficient diet) or soybean oil (control diet). The levels of docosahexaenoic acid [22:6 (n-3)] in retinal phospholipids were significantly decreased in n-3 deficient rats (35–42% of control levels). This was compensated by a rise in 22:5 (n-6), the total content of poly-unsaturated fatty acids (PUFA) remaining approximately constant. Adenylate cyclase activity was measured in retinal membrane preparations from dark-adapted or light-exposed rats. The enzyme activity was stimulated by DA and SKF 38393 in a light-dependent fashion. The activation was lower in rats exposed to light than in dark-adapted animals, suggesting a down-regulation of the DI DA receptors by light. The activation by guanine nucleotides and forskolin was also decreased in light-exposed rats. There was no significant effect of the dietary regimen on the various adenylate cyclase activities and their response to light. Furthermore, the guanine nucleotide- and DA-dependent adenylate cyclase activities of retinal membranes were found to be relatively resistant to changes in membrane fluidity induced in vitro by benzyl alcohol. The results indicate that in the absence of changes in total PUFA content, a decreased ratio of n-3 to n-6 fatty acids in membrane phospholipids does not significantly affect the properties of adenylate cyclase in the rat retina.
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  • 59
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Brain concentrations of salsolinol (SAL), a simple tetrahydroisoquinoline (sTIQ) condensation product of do-pamine (DA) and acetaldehyde, are reported to increase in chow-fed rats drinking ethanol/H2O ad libitum. However, our analyses showed that rat chow contains traces of SAL and, as previously reported, appreciable 3,4-dihydroxyphe-nylalanine (DOPA), a sTIQ precursor. To examine the effect of consumption of ethanol in a DOPA- and SAL-free diet on endogenous sTIQs, we analyzed two brain regions and blood plasma of rats undergoing prolonged intake (3 weeks and 23 weeks) of liquid diet containing 6.6% ethanol or iso-caloric carbohydrate. SAL and three other DA-related sTIQs were quantitated using capillary gas chromatography/mass spectrometry in the selected ion mode with deuterated standards. In accord with studies on ethanol/chow-fed rats. sTIQ concentrations in hypothalamus were elevated after 3 weeks of ethanol, although after 23 weeks, hypothalamic sTIQs were either unchanged or reduced (O-methylated SAL). Furthermore, sTIQ concentrations in corpus triatum and, with one exception, plasma were not altered by ethanol ingestion for either duration. (However, 23 weeks of ethanol intake significantly reduced the striatal concentrations of DA and its acid metabolite, presumably reflecting neurotoxicity.) Reasoning that DOPA in diet might underlie the reported ethanol-dependent increases in striatal sTIQs, we found that l-DOPA supplementation (500 μg/rat/day) of EtOH/Iiquid diet-fed rats for 13 weeks tended to increase striatal SAL. Overall, the data indicate that elevations in endogenous sTIQ concentrations due to prolonged ethanol intake depend on the brain region, duration of intake, and even associated dietary constituents. In that regard, the higher striatal SAL concentrations in rats drinking ethanol ad libitum could have been facilitated by DOPA and perhaps SAL consumed in lab chow.
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  • 60
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Modifications of plasma membrane acyl-linked phospholipid fatty acid composition were produced by supplementing the culture medium with essential fatty acids. The plasma membrane fraction was purified by Percoll gradient centrifugation from dissociated fetal rat brain cells grown in a serum-free culture medium. Both the concentration dependence and the time course of the modifications were examined. Supplementation of the medium with essential polyunsaturated fatty acid, linolenic acid (18:3ω3) or lin-oleic acid (18:2ω6), produced incorporation of the elongated and desaturated products of ω3 or ω6 class, respectively, i.e., the incorporation was class specific. Within each class, the most unsaturated and elongated members, i.e., terminal members, were preferentially incorporated until they reached a maximum concentration within 6–7 days. At higher concentrations of supplemented fatty acids, additional class specific incorporation in plasma membrane was produced by an increase in the concentration of intermediate members. At the same time, the concentration of monounsaturated fatty acids declined and that of saturated fatty acids remained unchanged. The modifications in fatty acid composition were reversible, with the time course similar to that of incorporation. The total plasma membrane phospholipid and sterol contents did not change with alterations of fatty acid composition, but did change with time in culture. This preparation should prove useful for investigating the role of polyunsaturated fatty acids in brain cell functions, including neuronal excitability.
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  • 61
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: To reveal more of the mechanism whereby ATP induces arachidonic acid (AA) mobilization in astrocytes, primary cell cultures prelabeled with [3H]AA were exposed to ATP and various analogs. Release of 3H was dose and time dependent and was inhibited by blocking ATP binding. The potencies of a range of ATP analogs in mobilizing AA were consistent with that predicted for the involvement of a P2Y-purinergic receptor. Mobilization of AA was not due to nonspecific cell permeabilization, as assessed by leakage of cytoplasmic lactate dehydrogenase. AA mobilization by ATP was reduced when mobilization of intracellular calcium was inhibited and in the absence of extracellular calcium. Thap sigargin, which induces release of intracellular calcium, evoked mobilization of AA and thromboxane formation, findings similar to the effects of ATP. These results suggest that ATP stimulates AA mobilization via a P2Y-purinergic receptor and that, although extracellular calcium is involved, mobilization of intracellular calcium activates phospholipase A2.
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  • 62
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A new sulfur-containing cyclic imino acid, cystathionine ketimine, has been detected in bovine cerebellum by gas chromatography, gas chromatography-mass spectrometry, and high pressure liquid chromatography procedures. Gas chromatography and gas-mass analyses are based on derivatization of endogenous cystathionine ketimine with diazomethane after a simple enrichment procedure. The high pressure liquid chromatography procedure takes advantage of the selective absorbance at 380 nm of the phenyl isothio-cyanate-ketimine interaction product. The concentration of this new sulfur imino acid found in a pool of four bovine cerebella is ∼0.5 nmol/g.
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  • 63
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We have investigated the presence of endogenous adenosine and of mechanisms for adenosine uptake and release in chick embryo retinal neurons and photoreceptors grown in purified cultures in the absence of glial cells. Simultaneous autoradiographic and immunocytochemical analysis showed that endogenous adenosine and the uptake mechanism for this nucleoside colocalize in practically all the photoreceptors, but only in ∼20% of the neurons. Approximately 25% of the neurons showed either immunocytochemical labeling or autoradiographic labeling, while 〉50% of the neurons were unlabeled with both techniques. [3H]Adenosine uptake was saturable and could be inhibited by nitrobenzylthioinosine and dipyridamole and by pretreatment of the [3H]adenosine with adenosine deaminase. Although these observations indicate that the uptake is specific for adenosine, only 35% of accumulated radioactivity was associated with adenosine, with the remaining 65% representing inosine, hypoxanthine. and nucleotides plus uric acid. Adenosine as well as several of its metabolites were released by the cells under basal as well as K+-stimulated conditions. Potassium-enhanced release was blocked by 10 mM CoCl2 or in Ca2+-free, Mg2+-rich solutions. The results indicate that retinal cells that synthesize, store, and release adenosine differentiate early during embryogenesis and are therefore consistent with a hypothetical role for adenosine in retinal development.
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  • 64
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Phosphate-activated glutaminase, glutamic acid decarboxylase, pyruvate dehydrogenase, succinic dehydrogenase, pH, and lactate were measured in frontal cortex and caudate nucleus of postmortem brains from cases of Alzheimer-type dementia (ATD), Down's syndrome, Huntington's disease, and one case of Pick's disease, as well as from sudden death and agonal controls. Lactate levels were higher and pH, phosphate-activated glutaminase, and glutamic acid decarboxylase levels were lower in the agonal controls than in the sudden death controls. Phosphate-activated glutaminase and glutamic acid decarboxylase were correlated with tissue pH and lactate, and also were reduced by in vitro acidification, suggesting that the low activities of these enzymes in agonal controls were related to decreased pH consequent upon lactate accumulation. Compared with control tissues at the same pH, phosphate-activated glutaminase and glutamic acid decarboxylase were unaltered in ATD and Down's frontal cortex and reduced in Huntington's caudate nucleus, and glutamic acid decarboxylase was reduced in Huntington's frontal cortex. These data suggest that GABAergic neurons are not affected in ATD and confirm the GABAergic defect in Huntington's disease. Pyruvate dehydrogenase and succinic dehydrogenase activities were the same in agonal controls and sudden death controls and were unaffected by acid pH and lactate in vitro, and pyruvate dehydrogenase was not correlated with pH or lactate. Reduced pyruvate dehydrogenase in frontal cortex of individual ATD, Down's, and Pick's cases. and in the caudate nucleus of Huntington's and Down's cases, was accompanied by gliosis/neuron loss. We conclude that decreased pyruvate dehydrogenase reflects neuronal loss.
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  • 65
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Binding activity of [3H]thienylcyclohexylpiperidine was examined using rat brain synaptic membranes treated with Triton X-100. This compound is proposed to be a noncompetitive antagonist for the N-methyl-d-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors. The activity decreased in proportion to increasing concentrations of the detergent up to 0.08%. In vitro addition of l-glutamate (Glu) partially restored the decreased activity caused by this Triton treatment, whereas further addition of glycine (Gly) entirely reversed the loss of activity to the level found in membranes extensively washed but not treated with a detergent. These stimulatory effects were found to be due to the acceleration of the association of ligand. The rank order of potentiation of the activity coincided well with that of the affinity for the NMDA-sensitive subclass among numerous Glu analogs. The potentiation by Gly as well as Glu was invariably prevented by competitive NMDA antagonists, such as dl-2-amino-5-phosphonovalerate and (×)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate, but not by strychnine. No significant difference was observed between pharmacological profiles of the activities in synaptic membranes treated and not treated with Triton X-100, except haloperidol. The potency of this σ-ligand to inhibit the activity was greatly reduced by the Triton treatment in the presence of both Glu and Gly. These results suggest that the regulatory properties of Triton-treated synaptic membranes remain unchanged in terms of the interaction within the NMDA receptor complex.
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  • 66
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    Topics: Medicine
    Notes: Abstract: Human neuronal brain cultures established from 12- and 14-week-old fetuses synthesize and secrete urokinase-type plasminogen activator (uPA) and limited amounts of tissue-type plasminogen activator (tPA). These cells also produce and secrete the endothelial cell-type PA inhibitor (PAII), which forms sodium dodecyl sulfate-stable tPA/PAI-I complexes in the culture medium. Immunocytochemistry shows a predominant localization of uPA, tPA, and PAI-1 in neuronal cells, with only a very weak positivity detectable in the few glial cells present in these cultures. The protein kinase C (PKC) activator 12-0-tetradecanoylphorbol 13-ac-etate (TPA) stimulates the synthesis of both uPA and PAI-I, resulting in a final increase in the plasmin-generating capacity of neuronal cell cultures. No significant effect is observed, however, when cells are treated with the TPA analogue 4a-phorbol 12,13-didecanoate, which is inactive as a PKC inducer, or with the neurotrophic polypeptide basic fibroblast growth factor. These data represent the first characterization of the plasmin-generating system in human fetal brain neurons and suggest a role for PKC in the modulation of uPA and PAI-I synthesis.
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  • 67
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    Journal of neurochemistry 55 (1990), S. 0 
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    Topics: Medicine
    Notes: Abstract: Several major proteins of synaptic vesicles from rat or cow brain sediment as a large complex on sucrose density gradients when solubilized in nonionic detergents. A vacuolar H+-ATPase identified by sensitivity to bafilomycin A1 appears to be associated with this oligomeric protein complex. Two subunits of this complex, synaptic vesicle proteins S and U, correspond to the 57-kDa (B) and 39-kDa accessory (Ac39) subunits, respectively, of bovine chromaffin granule vacuolar H+-ATPase as shown by Western immunoblot analysis. The five subunits of the oligomeric complex constitute −20% of the total protein of rat brain synaptic vesicles. Taken together, these results strongly suggest that the abundant, multisubunit complex partially purified from brain synaptic vesicles by density gradient centrifugation is a vacuolar H+-ATPase. Bafilomycin A1 completely blocks proton pumping in rat brain synaptic vesicles as measured by [14C]methylamine uptake and also blocks catecholamine accumulation measured by [3H]dopamine uptake. Moreover, ATPase activity, [14C]methylamine uptake, and [3H]dopamine uptake are inhibited by bafilomycin A1 at similar I50 values of ∼ 1.7 nmol/mg of protein. These findings indicate that the vacuolar H+-ATPase is essential for proton pumping as well as catecholamine uptake by mammalian synaptic vesicles.
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  • 68
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Myelin basic protein isolated from normal human brain was resolved into its various components (charge isomers) by CM-52 column chromatography. Two of the components, C-1 and C-4, were phosphorylated in vitro with a soluble preparation of brain protein kinase C. For each component, the peptides phosphorylated were identified. In both components a major site of phosphorylation was found at Ser7 in the N-terminal portion of the protein. Both the specific activity and the rate of phosphorylation were greatest at this site in both components when compared with the other sites. The rate of phosphorylation of peptide 5-I3 was ∼10 times greater than that of any of the other peptides derived from C-1, while the rate of phosphorylation of peptide 5-I3 derived from C-4 was 10-20 times greater than that of any of the other peptides derived from C-4. In addition, peptide 5-13, which contained a major phosphorylation site in both C-1 and C-4, was phosphorylated at a faster rate in C-4 (460 cpm/nM/min) compared with C-1 (285 cpm/nM/min). Both the specific activity and the rate data presented in the present communication were correlated with the proportion of p-structure in a previous study. In that study, C-1, which contained about 13% & structure before phosphorylation, increased to −40% after phosphorylation. Construction of a model peptide of this N-terminal region, which included the phosphorylation site at Ser7, demonstmted that the β structure was stabilized by electrostatic interactions between the phosphate on Ser7 and the guanidy groups of Arg5 and Arg9. On the other hand, phosphorylation of C-4, which was already −34% P-structure, was twice as fast at Ser7 as for C-I, suggesting that the preexistence of 8-structure in the molecule facilitated phosphorylation at this site. In previous studies phosphorylation of C-I was shown to decrease vesicle aggregation, which we concluded to be the result of electrostatic repulsion between the phosphate on the protein and that of the lipid. The present data suggest that phosphorylation of some specific site may be playing an important role in the conformation of the protein.
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  • 69
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The potential for cross-talk between the adenyl cy-clase and phosphoinositide (PPI) lipid second messenger system was investigated in astrocytes cultured from neonatal rat brain. Glutamate-stimulated PPI turnover, measured by the formation of total inositol phosphates from myo-[3H]inositoI-labeled lipids, was inhibited in a concentration-dependent manner by the elevation of intracellular cyclic AMP levels produced either by stimulation of the isoproter-enol receptor linked to adenyl cyclase or by its direct activation by forskolin. N6,2′-O-Dibutyryl cyclic AMP, an analogue that can also activate cyclic AMP-dependent kinase, inhibited glutamate-stimulated PPI turnover in a concentration-dependent manner as well, a result suggesting that cyclic AMP-dependent kinase is involved in mediating the inhibition. Inclusion of an inhibitor of cyclic AMP-dependent kinase, l-(5-isoquinolinesulfonyl)-2 methylpiperazine dihy-drochloride or N-(2-guanidinoethyl)-5-isoquinolinesulfon-amide hydrochloride, blocked the cyclic AMP-mediated inhibition in a concentration-dependent manner, a finding further supporting this hypothesis. The site of inhibition of the phosphoinositol lipid pathway by cyclic AMP was probed using a digitonin-permeabilized cell system. Guanosine 5′-O-(3-thiotriphosphate), a nonhydrolyzable analogue of GTP, stimulated PPI turnover and potentiated glutamate-stimulated PPI turnover, and guanosine 5′-O-(3-thiodiphosphate) inhibited glutamate-stimulated PPI turnover in these cells, results providing evidence that glutamate receptors are coupled to phospholipase C by a guanine nucleotide binding protein in astrocytes. N6,2′-O-Dibutyryl cyclic AMP and agents that elevate cyclic AMP levels inhibited the PPI turnover stimulated by guanosine 5′-O-(3-thiotriphosphate), as well as that potentiated by guanosine 5′-O-(3-thiotriphos-phate) in the presence of glutamate, results suggesting that the cyclic AMP-dependent inhibition occurs at or distal to the putative guanine nucleotide binding protein. Because basal PPI turnover was not altered by elevation of cyclic AMP levels, direct inhibition of phospholipase C is unlikely.
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  • 70
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    Journal of neurochemistry 55 (1990), S. 0 
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Previously, we had suggested that heparan sulfate (HS) makes some contribution to a flat-shaped morphology of PC12D cells. Therefore, we carried out quantitative and qualitative analyses of glycosaminoglycans (GAGs), the polysaccharide moiety of proteoglycans, during neuritogenesis in PC12 cells that is induced by nerve growth factor (NGF). (a) In PC12 cells, NGF induced a flat-shaped morphology with a few short processes after 3 days of culture, and then it elicited short and long neurites after 6 (in ∼30% of cells) and 9 (in 60–70%) days of culture, respectively, (b) HS and chondroitin sulfate (CS) were detected in the cell layer at all times. Only CS was found in the medium at 3 and 6 days, whereas a low level of HS, in addition to CS, was detectable on day 9. (c) In the NGF-treated cultures, the amounts of cell-associated HS per cell were two to three times as high as those in the respective nontreated cultures at all times, whereas the amount based on phospholipid was about twofold higher after 3 days of culture. (d) The levels of HS labeled with [35S]sulfate during the last 48 h of the culture were 1.5-to twofold higher in the NGF-treated cultures than in the respective controls at any time. (e) The amount of cell-associated CS per cell (or per unit of phospholipid), but not of labeled CS per cell, was transiently enhanced at 3 days in culture with or without NGF. At all times, NGF treatment caused an increase in the levels of total and [35S]sulfate-labeled CS associated with the cells and released into the medium, (f) NGF enhanced the amount of N-sulfation of glucosamine residues of HS at all times, but it did not change the ratio of 4-sulfate units to 6-sulfate units in CS. (g) At 3 days in culture, the uptake of [35S]sulfate by PC12 cells was lower in the NGF-treated culture than in the nontreated control. (h) In chase experiments, the percentage of unrecovered CS was about twofold higher in the NGF-treated culture than in the non-treated control. These results suggest that the enhanced synthetic activity and the accumulation of GAGs as well as the structural change of HS induced by NGF occur preceding the neurite elongation from PC12 cells. Also, it is suggested that the increase in content of HS is closely correlated with the morphological change from round to flat in PC12 cells.
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Tyrosine hydroxylase (TH)-mRNA, assayed by in situ hybridization combined with TH immunocytochemistry, showed a selective increase in the ventral tegmental area (A-10) but not in the substantia nigra (A-9) midbrain dopaminergic (DAergic) neurons 3 days after reserpine treatment. TH-mRNA in locus ceruleus noradrenergic (A-4) neurons was increased by reserpine, as confirmed by RNA blot hybridization. These findings show that TH-mRNA is differentially regulated in midbrain DAergic neurons in response to reserpine.
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  • 72
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The cyclic GMP (cGMP) content was rapidly (〉30 s) increased by serotonin [5-hydroxytryptamine (5-HT)] (EC50= 10 μM), and the increase lasted for 〉 10 min in NG108–15 cells. The 5-HT-induced elevation of cGMP level (EC50= 10 μM) at 20 s (“fast” elevation) was inhibited by ICS 205–930 or MDL 72,222 and by Ca2+ deficiency in the reaction medium but not by organic Ca2+ antagonists. The 5-HT effect at 10 min (“slow” elevation) was not inhibited by several antagonists for 5-HT receptors of the IA, IB, IC., ID, 2, and 3 subtypes and was independent from external Ca2+ concentration. The fast and slow effects of 5-HT were similar to the effects of bradykinin and atrial natriuretic peptide (ANP), respectively, in aspects of both Ca2+ dependency and time course of the effects. Bradykinin transiently stimulated formation of inositol phosphates as well as accumulation of cGMP, a finding suggesting that intracellular Ca2+ is involved in bradykinin-induced cGMP accumulation as shown in the fast response to 5-HT. ANP. an activator of membrane-associated guanylate cyclase (mGC), slowly (∼60 s) increased the cGMP content (EC50= 10 nAf), a result lasting for 〉10 min, and the effects were independent from external Ca2+, as shown in the slow response to 5-HT. 5-HT and ANP did not induce formation of inositol phosphates. These results suggest that (a) the fast effects of 5-HT on cGMP level elevation are mediated by 5-HT3 receptors, which activate cytosolic guanylate cyclase through Ca2+ entry via ion channels other than voltage-sensitive Ca24 channels, and (b) the slow effects seem to be due to an unidentified subtype of 5-HT receptor that activates ANP-sensitive mGC.
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  • 73
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 74
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Some data on the concentration range of response and the concentration for half-response (EC50) of γ-aminobutyric acid (GABA) for the GABAA receptor are reviewed and compared. An analysis of the 36CI− flux assay demonstrates that both the EC50 and the slope of a Hill plot depend on the ion influx or efflux assay time. The effects of depletion of the 36CI− concentration gradient during the assay and of receptor desensitization on the result for a range of assay times are considered. The EC50 can be decreased by orders of magnitude by increasing the assay time. The EC50 measured in a finite time is less than the half-response concentration for the response(s) of the receptor. The extent of this difference depends on the receptor concentration per internal volume. The maximal decrease of EC50 depends on the rate of receptor desensitization. The computer simulations showed that a GABAA receptor with a half-response concentration of 100 μM GABA can give 36CI− flux measurements with an EC50 value 100-fold lower.
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  • 75
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The purpose of the present study is to clarify the effects of hypoxia on catecholamine release and its mechanism of action. For this purpose, using cultured bovine adrenal chromaffin cells, we examined the effects of hypoxia on high (55 mM) K+-induced increases in catecholamine release, in cytosolic free Ca2+ concentration ([Ca2+]i), and in 45Ca2+ uptake. Experiments were carried out in media pre-equilibrated with a gas mixture of either 21% O2/79% N2 (control) or 100% N2 (hypoxia). High K+-induced catecholamine release was inhibited by hypoxia to ∼40% of the control value, but on reoxygenation the release returned to control levels. Hypoxia had little effect on ATP concentrations in the cells. In the hypoxic medium, [Ca2+]i (measured using fura-2) gradually increased and reached a plateau of ∼1.0 μM at 30 min, whereas the level was constant in the control medium (∼200 nM). High K+-induced increases in [Ca2+]I were inhibited by hypoxia to ∼30% of the control value. In the cells permeabilized by digitonin, catecholamine release induced by Ca2+ was unaffected by hypoxia. Hypoxia had little effect on basal 45Ca2+ uptake into the cells, but high K+-induced 45Ca2+ uptake was inhibited by hypoxia. These results suggest that hypoxia inhibits high K+-induced catecholamine release and that this inhibition is mainly the result of the inhibition of high K+-induced increases in [Ca2+]i subsequent to the inhibition of Ca2+ influx through voltage-dependent Ca2+ channels.
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  • 76
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In this report, we show that under conditions designed to provide an initially uniform incorporation of [3H]inositol into mouse and guinea pig cerebral cortical slices prior to agonist stimulation, the accumulation of 3H-inositol phosphates (3H-InsPx, x = 1–4) induced by histamine in mouse and guinea pig cerebral cortical slices increased in a quasilinear manner with increasing added calcium. Raising the ambient calcium ion concentration failed to reduce the adenosine receptor-mediated inhibition of the histamine-induced 3H-InsPx response in mouse cerebral cortical slices. Similarly, the potentiation of the histamine response by adenosine receptor activation in guinea pig cerebral cortical slices was unaffected by lowering the added calcium ion concentration. The presence of the calcium ionophore A23187 (33 μM) produced 3H-InsPx responses in both mouse and guinea pig cerebral cortical slices, which were not affected by the presence of the stable adenosine analogue 2-chloroadenosine. A23187 also potentiated the accumulation of 3H-InsPx induced by histamine in both species. Both the inhibitory and potentiatory modulations of the histamine response by 2-chloroadenosine in mouse and guinea pig, respectively, were still apparent in the presence of A23187. These results indicate that the histamine-induced 3H-InsPx accumulations in both mouse and guinea pig cerebral cortical slices are sensitive to variations in calcium ion concentrations. However, the adenosine receptor modulations of the histamine responses are relatively insensitive to fluctuations in either extra-or intracellular calcium ion concentrations, and thus cannot be mediated by effects on calcium ion movements.
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  • 77
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: After a relatively mild course of uncontrollable shocks, two distinct groups of rats can be defined in terms of their performance in learning to escape from a controllable stressor. Response-deficient (RD) rats do not learn to terminate the controllable stressor, whereas nondeficient (ND) rats learn this response as readily as do untreated control rats. The current studies were designed to determine the neu-rochemical correlates of the behavioral differences between these groups of rats. The major findings concerned postsyn-aptic β-adrenergic effects in the hippocampus of RD rats. These included an up-regulation of β-adrenergic receptors and, in parallel experiments, an increase in the sensitivity of adenylyl cyclase to stimulation by norepinephrine. There was no difference in brain levels of catecholamines between the three groups of rats. A statistically significant increase in levels of 5-hydroxytryptamine was noted in the hippocampus and hypothalamus of RD rats as compared to levels in ND rats, but no significant differences were measured between groups of rats in terms of S1 or S2 serotonergic receptor binding. These results implicate both β-adrenergic and serotonergic mechanisms in the behavioral deficit caused by uncontrollable shock.
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  • 78
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Vasoactive intestinal peptide (VIP) is known to mimic the effects of β-adrenergic receptor stimulation in the rat pineal, including marked potentiation by α1-adrenergic receptor stimulation, and to cause increased melatonin synthesis. In contrast, the chick pineal does not respond to β-adrenergic stimulation, and melatonin synthesis is inhibited by norepinephrine via an α2-adrenergic receptor. The present experiments show that chick pineal cells in primary culture do, however, respond to VIP with increased melatonin production. The effect of VIP was inhibited by addition of norepinephrine or of nitrendipine or by exposing the cells to “unexpected” white light. Stimulation by VIP was enhanced by addition of forskolin or Bay K 8644 but not by α1adrenergic receptor stimulation. Although stimulation by VIP appears similar in the chick pineal to that seen in the rat pineal and other systems, “dual-receptor regulation,” at least with α1-adrenergic receptors, appears to be absent.
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  • 79
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Using antibodies raised against human platelet phenol sulfotransferase (PST), immunohistochemical studies were performed to determine the cellular localization of PST in several areas of human brain. In the hippocampus PST immunoreactivity was localized in both the pyramidal and nonpyramidal neurons and was in greatest abundance in the CA2 and CA3 areas. In the striatum the immunoreactivity was most predominant in the large neurons of the globus pallidus and in the medulla the staining was scattered throughout the neurons of the raphe nucleus and the reticular formation. The selective presence of PST in the neurons of the CNS raises the issue as to the role of this enzyme in sulfating neurotransmitters because PST has been shown to be capable of conjugating a variety of neurotransmitters including the catecholamines as well as the tyrosine moiety of a number of small peptides such as enkephalin and cholecystokinin.
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  • 80
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We have determined the whole promoter sequence and the transcriptional startpoint of the mouse glial fibrillary acidic protein (GFAP) gene and characterized the promoter function. We found that the cis elements for astrocyte specific expression are located within 256 bp from the transcription startpoint. We defined by DNase I footprinting assay three trans-acting factor binding sites (GFI, GFII, and GFIII) using brain or C6 astrocytoma nuclear extracts. GFI, GFII, and GFIII have AP-2, NFI, and cyclic AMP-responsive element motifs, respectively. Mutations in GFII drastically decreased the promoter activity. Base substitution in GFI and GFIII abolished the cell-specific expression, resulting in the GFAP promoter expression even in some non-GFAP-producing cells.
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  • 81
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The structurally similar compounds staurosporine and K252a are potent inhibitors of protein kinases. K252a has previously been reported to inhibit most or all of the effects of nerve growth factor (NGF) on PC12 pheochromocytoma cells, and staurosporine has been reported both to inhibit and to mimic NGF-induced neurite outgrowth from a PC12 cell subclone in a dose-dependent manner. We have studied the interactions of these agents with each other, with NGF, and with forskolin, an activator of adenylate cyclase, on the parent PC12 cell line and on normal neonatal and adult rat chromaffin cells. Staurosporine alone or in conjunction with forskolin induces outgrowth of short neurites from PC12 cells but does not substitute for NGF in promoting cell survival. It does not abolish NGF-induced neurite outgrowth but does reverse the effects of NGF on catecholamine synthesis. K252a abolishes NGF-induced neurite outgrowth but only partially decreases outgrowth induced by NGF plus forskolin. It does not inhibit neurite outgrowth produced by staurosporine or staurosporine plus forskolin. These findings with PC12 cells suggest that staurosporine might act downstream from K252a and NGF on components of one or more signal transduction pathways by which NGF selectively affects the expression of certain traits. Both neonatal and adult rat chromaffin cells show dramatic flattening and extension of filopodia in response to staurosporine, an observation suggesting that some of the same pathways might remain active in cells that do not exhibit a typical NGF response. Only a small amount of neurite outgrowth is observed, however, and only in neonatal cultures. Staurosporine might be useful in studying both the actions of NGF and the ways in which those actions are altered in the course of normal development and tumor formation.
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  • 82
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Monoamine oxidase (MAO) A and B play important roles in the metabolism of biogenic amines. Northern analysis using 32P-labeled subfragments of human liver MAO A and B cDNA clones detected a 5- and a 3-kb transcript, respectively, in most human tissues examined. However, fetal heart and thymus express minute amounts of MAO A transcript, whereas fetal brain, muscle, thymus, spleen, meninges, and placenta express minute amounts of MAO B transcript. Small intestine and placenta express, in addition to the MAO A 5-kb transcript, a 2-kb transcript, which may arise from an alternative polyadenylation site. MAO A and B transcripts are expressed in similar regions of adult human brain. The highest concentrations of these transcripts were located in frontal cortex and locus coeruleus. This study demonstrates the tissue-specific distribution of the MAO genes and will provide insight into the physiological functions of MAO A and B.
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  • 83
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian retina, where it serves many roles in establishing complex response characteristics of ganglion cells. We now provide biochemical and physiological evidence that at least three subclasses of GABA receptors (A1, A2, and B) contribute to different types of synaptic integration. Receptor binding studies indicate that approximately three-fourths of the total number of [3H]GABA binding sites in retina are displaced by the GABAA receptor antagonist, bicuculline, whereas one-fourth are displaced by the GABA-B receptor agonist, baclofen. GABAA receptors can be described by a three-site binding model with KD values of 19 nM, 122 nM, and 5.7 μM. Benzodiazepines and barbiturates potentiate binding to the GABAA site, which suggests that significant numbers of GABAA receptors are coupled to regulatory sites for these compounds and thus are classified as GABAA1 receptors. The response to pentobarbital appears to involve a conversion of low-affinity sites to higher-affinity sites, and is reflected in changes in the densities of sites at different affinities. Functional studies were used to establish which of the different receptor subclasses regulate release from cholinergic amacrine cells. Our results show that GABA suppresses light-evoked [3H]acetylcholine release via GABAA2 receptors not coupled to a benzodiazepine or barbiturate regulatory site, and enhances release via GABAB receptors. GABAA1 sites do not appear to control acetylcholine release in rabbit retina.
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  • 84
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-d-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/ kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-d-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.
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  • 85
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We examined the changes in the molecular species of brain ethanolamine glycerophospholipids of monkeys fed diets containing widely ranging amounts of n-3 fatty acids. Two groups of rhesus monkeys were fed pre- and postnatally either a control diet (soy oil; containing 8% of fatty acids as 18:3n-3) or a deficient diet (safflower oil; containing 〈0.3% 18:3n-3). The brains of these animals were analyzed at 22 months of age. A third group of monkeys was fed the safflower oil diet to 22 months of age and then switched to a fish oil diet (28% long-chain n-3 fatty acids) for 1–2 years before autopsy. The molecular species of the diacyl, alkylacyl, and alkenylacyl ethanolamine glycerophospholipids from frontal cortex were separated by HPLC. A total of 24 molecular species were identified. Fatty acids in the sn-2 position differed markedly among the diet groups, but the sn-1 position always contained only 16:0, 18:0, or 18:1. In the diacyl subclass of the control brain, the n-3 molecular species represented 41% of total and the n-6 species 45%, whereas in the deficient brain the n-3 molecular species decreased to 9% and n-6 molecular species increased to 77%. The fatty acid 22:5n-6 did not replace 22:6n-3 in a symmetrical fashion in the molecular species of the deficient brain. In the brains of the fish oil-fed monkeys, the n-3 molecular species amounted to 61% and n-6 molecular species were reduced to 25%. The species 18:1–22:6, 16:0–22:6, and 18:0–22:6 generally changed proportionally in response to diet. However, 18:1–20:4, 16:0–20: 4, and 18:0–20:4 responded differently. The fish oil diet led to an increase in the proportion of 18:1–20:4 in the alkenylacyl subclass, whereas 16:0–20:4 and 18:0–20:4 decreased. Thus, total species containing sn-1 18:1 increased at the expense of sn-1 16:0 in the fish oil animals. Regardless of diet, each subclass of ethanolamine glycerophospholipid showed a strikingly different ratio of sn-1 16:0 to 18:0 to 18:1 for a given sn-2 fatty acid. In conclusion, the different diets had profound qualitative and quantitative effects on the molecular species of brain phospholipids, and these changes have implications for possible functional changes.
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  • 86
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The acute administration of pentylenetetrazol (PTZ; 25–75 mg/kg i.p.) failed to modify the specific binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to membrane preparations from the cerebral cortex of the rat. In contrast, the repeated administration of PTZ (30 mg/kg i.p., three times a week for 12 weeks) reduced by 26% the density of [33S]TBPS binding sites without modifying the dissociation constant. This effect was observed 3 days after the last PTZ administration. A parallel reduction of 7-amino-butyric acid (GABA)-stimulated 36CI− uptake was measured in the cerebral cortex of PTZ-treated rats 3 days after the last injection. The repeated administration of PTZ produced sensitization to the drug, or chemical kindling. In fact, no convulsions were observed in the first week of treatment, but all the animals became sensitized to PTZ by the 12th week. The results are consistent with the hypothesis that chronic treatment with PTZ at a subconvulsant dose causes a decrease in GABA-coupled chloride channel activity that may be related to the chemical kindling produced by this compound.
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  • 87
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In vivo voltammetry with carbon fiber electrodes was used to assess extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) levels in striatum, nucleus accumbens. and anteromedial prefrontal cortex of freely moving rats subjected to altered motor activity or anxiogenic stimuli. Forced locomotion on a rotarod for 40 min caused an increase in extracellular DOPAC levels in the striatum and to a lesser extent in the nucleus accumbens but not in the prefrontal cortex. Subcutaneous injection of the anxiogenic agent methyl-β-carboline carboxylate (10 mg/kg) increased extracellular DOPAC levels to a similar extent in prefrontal cortex and nucleus accumbens. Immobilization for 4 min augmented dopamine (DA) metabolism preferentially in the nucleus accumbens and to a lesser extent in the prefrontal cortex. Tail-pinch caused a selective activation of DA metabolism in the nucleus accumbens. None of these stimuli altered extracellular striatal DOPAC levels. These results confirm the involvement of dopaminergic systems projecting to the striatum and nucleus accumbens in motor function and suggest that mesolimbic and mesocortical dopaminergic systems can be specifically activated by certain kinds of anxiogenic stimuli; the relative activation of either of these latter systems could depend primarily on the nature (sensory modality, intensity) of the acute stressor.
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  • 88
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: This study provides evidence that apolipoprotein-A-I (apo-A-I), derived from fish plasma and nerve, has heparin binding activity. We have shown previously that injury in a regenerative CNS, such as that of fish optic nerves, leads to increased levels of apo-A-I in media conditioned by these nerves, as compared with media conditioned by noninjured nerves. In the present study, we have purified and characterized apo-A-I from both fish plasma and optic nerves. Sequence analysis of the 15 N-terminal amino acids revealed that at least 14 amino acids are identical in these two purified apo-A-I samples. The purified apo-A-I derived from both fish plasma and optic nerves binds to heparin. Binding measurements using [3H]heparin followed by Scatchard analysis revealed that apo-A-I binds to heparin with relatively low affinity (KD= 2.8 × 10−6M). Results are discussed with respect to the possibility that accumulation of apo-A-I in the extracellular matrix of fish optic nerves is made possible via heparin binding, like that to apolipoprotein-E in mammals.
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  • 89
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    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The concentrations of free choline in blood plasma from a peripheral artery and from the transverse sinus, in the CSF, and in total brain homogenate, have been measured in untreated rats and in rats after acute intraperitoneal administration of choline chloride. In untreated rats, the arteriovenous difference of brain choline was related to the arterial choline level. At low arterial blood levels (〈10 μM) as observed under fasting conditions, the arteriovenous difference was negative (about -2 μM), indicating a net release of choline from the brain of about 1.6 nmol/g/min. In rats with spontaneously high arterial blood levels (〉 15 μM), the arteriovenous difference was positive, implying a marked net uptake of choline by the brain (3.1 nmol/g/min). The CSF choline concentration, which reflects changes in the extracellular choline concentration, also increased with increasing plasma levels and closely paralleled the gradually rising net uptake. Acute administration of 6, 20, or 60 mg of choline chloride/kg caused, in a dose-dependent manner, a sharp rise of the arterial blood levels and the CSF choline, and reversed the arteriovenous difference of choline to markedly positive values. The total free choline in the brain rose only initially and to a quantitatively negligible extent. Thus, the amount of choline taken up by the brain within 30 min was stored almost completely in a metabolized form and was sufficient to sustain the release of choline from the brain as long as the plasma level remained low. We conclude that the extracellular choline concentration of the brain closely parallels fluctuations in the plasma level of choline. Moreover, the often described release of choline from the brain as reflected by the negative arteriovenous difference of brain choline is not a steady-state phenomenon. Instead, the uptake of choline into and the release of choline from the brain seem to be in dynamic equilibrium that is closely related to the plasma choline level and, consequently, to nutritional choline uptake.
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  • 90
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Uptake of the immunosuppressive lipophilic peptide cyclosporin A has been measured by a number of techniques. The brain uptake index (BUI) technique in the rat yields only a small BUI value that is not significantly different from that of sucrose and mannitol and is comparable to other published BUI values for this compound. Brain perfusion studies in the guinea pig produce a unidirectional cerebrovascular permeability constant (Kin) of 1.2 ± 0.28 μg−1 min−1 for the hippocampus. Intravenous bolus injection techniques also in the guinea pig characteristically produce a larger Kin value of 2.53 ± 0.38 μg−1 min−1 for the same brain region, even after a correction for the inulin space of the tissue has been made. Apparent penetration of cyclosporin A into the cerebrospinal fluid (CSF) determined with the intravenous bolus injection technique is small with a Kin of 0.79 ± 0.07 μ g−1 min−1. However it is suggested that the radioactivity present in CSF is largely tritiated water. Studies with cultured cerebral endothelial cells from the rat have also been carried out and show that the cultured cells take up and accumulate cyclosporin A in vitro, achieving a tissue-to-medium ratio of 20 after 25 min of incubation. It is suggested that cyclosporin A is primarily taken up from lipoprotein at the blood-brain interface but, because of tight junctions at the blood-brain and blood-CSF barriers, becomes effectively trapped in the cerebral endothelial cells and the choroid plexus.
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  • 91
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Pretreatment of striatal neurons from mouse embryos in primary culture with 17β-estradiol (10−9M, 24 h) enhanced the ADP-ribosylation of Gαo,i proteins catalyzed by pertussis toxin (PTX). As estimated by quantitative ADP-ribosylation of Gαs with cholera toxin and immunoblot experiments using anti-Gαo and anti-Gβ sera, 17β-estradiol pretreatment did not modify the levels of the major GTP-binding protein (G protein) constituent subunits Gαs, Gαo, and Gβ. Thus, 17β-estradiol should induce a qualitative modification of these G proteins, perhaps by stabilizing the association of the heterotrimers Gαo,iβγ, which are the targets of PTX. Such a hypothesis is in agreement with observations indicating that 17β-estradiol both suppressed the D2 dopamine- and opiate receptor-induced inhibitions of adenylate cyclase activity and enhanced the positive coupling between biogenic amine receptors (D1 dopamine, β-adrenergic, and A2 adenosine) and adenylate cyclase. In addition, PTX pretreatment, which is known to uncouple receptors associated with Go,i proteins and thus to impair the dissociation of the heterotrimers Gαo,iβγ, mimicks the effects of the steroid on the responses of adenylate cyclase to inhibitory and stimulatory agonists. Finally, the chemical specificity of the steroids was the same in the ADP-ribosylation as in the adenylate cyclase experiments: Testosterone (10−9M) mimicked the effects of 17β-estradiol, whereas 17α-estradiol, progesterone, and dexamethasone did not. Because 17β-estradiol enhanced uniformly the PTX-catalyzed ADP-ribosylation of Gαo and Gαi proteins, it can be expected that transducing systems other than adenylate cyclase involving these G proteins, such as ionic channels or phospholipases, are also affected by the steroid pretreatment of striatal neurons.
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  • 92
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    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: To monitor the fate of the synaptic vesicle membrane compartment, synaptic vesicles were isolated under varying experimental conditions from blocks of perfused Torpedo electric organ. In accordance with previous results, after low-frequency stimulation (0.1 Hz, 1,800 pulses) of perfused blocks of electric organ, a population of vesicles (VP2 type) can be separated by density gradient centrifugation and chromatography on porous glass beads that is denser and smaller than resting vesicles (VP1 type). By simultaneous application of fluorescein isothiocyanate-dextran as extracellular volume marker and [3H]acetate as precursor of vesicular acetylcholine, and by identifying the vesicular membrane compartment with an antibody against the synaptic vesicle transmembrane glycoprotein SV2, we can show that the membrane compartment of part of the synaptic vesicles becomes recycled during the stimulation period. It then contains both newly synthesized acetylcholine and a sample of extra cellular medium. Recycled vesicles have not incorporated the presynaptic plasma membrane marker acetylcholinesterase. Cisternae or vacuoles are presumably not involved in vesicle recycling. After a subsequent period of recovery (18 h), all vesicular membrane compartments behave like VP1 vesicles on subcellular fractionation and still retain both volume markers. Our results imply that on low-frequency stimulation, synaptic vesicles are directly recycled, equilibrating their luminal contents with the extracellular medium and retaining their membrane identity and capability to accumulate acetylcholine.
    Type of Medium: Electronic Resource
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  • 93
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neuropathy target esterase (NTE) is the suggested “target” molecule involved in the initiation of organophosphorus-induced delayed polyneuropathy. Sciatic nerve NTE was separated into particulate (P-NTE) and soluble (S-NTE) fractions by ultracentrifugation at 100,000 g for 1 h in 0.32 M sucrose and compared with the corresponding brain extract. Total sciatic NTE activity was 80–100 nmol/min/g tissue from which 50–60% was recovered in the soluble supernatant fraction and the remaining 40–50% in the pellet fraction. About 90% of brain tissue activity (∼ 1,800 nmol/min/g tissue) was recovered as P-NTE. A similar distribution was obtained when more drastic centrifugation without sucrose was performed. P-NTE and S-NTE were distributed with the membrane and cytosolic markers assayed, respectively, glucose-6-phosphatase, Na+,K+-ATPase, 5′-nucleotidase, phospholipids, and lactate dehydrogenase. When the pH during the centrifugation was increased from 6.4 to 11, recovered P-NTE activity decreased from 1,750 to 118 nmol/min/g tissue for brain and from 31 to 12 nmol/min/g for sciatic nerve. However, S-NTE activity and total nonfractionated control activity were only slightly affected by the same pH treatment. The distribution pattern encountered may be better understood as representing two different proteins than an equilibrium between soluble and membrane-bound portions of a single protein, with P-NTE activity depending on a membrane factor from which it is separated through fractionation at high pH. The titration curve corresponding to inhibition by mipafox was studied over the 0.1–200 μM range, in the presence of 40 μM paraoxon, and data obtained were fitted to models of one or two exponential mipafox-sensitive components plus a resistant component. Mipafox-resistant activity was 38 and 52% of total paraoxon-resistant activity for the particulate and soluble fractions, respectively. Particle data suggest that P-NTE contains mainly one component with I50 of ∼5.4–7.3 μM, this representing 〉85% of total mipafox-sensitive activity. However, the soluble fraction data fit better to two sensitive components: high- and low-mipafox-sensitive components with I50 of 4.9 and 43 μM, representing 35 and 65% of total paraoxon-resistant activity, respectively.
    Type of Medium: Electronic Resource
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  • 94
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The characteristics of glycosylation of a brain-specific glycoprotein, 1D4 antigen, and the epitope recognized by its monoclonal antibody were studied. Removal of high-mannose and hybrid types of N-linked oligosaccharides by treatment with endoglycosidase H converted the molecular mass of the 1D4 antigen from 89 kDa to 78 kDa, but did not affect its reactivity with the 1D4 monoclonal antibody. Removal of all types of N-linked oligosaccharides by treatment with glycopeptidase F or removal of both N- and O-linked oligosaccharides by chemical treatment caused both reduction of the molecular mass of the antigen to 63 kDa and loss of its reactivity with the monoclonal antibody. These results suggest that the 1D4 monoclonal antibody recognizes a complex-type oligosaccharide-related epitope specific for the 1D4 antigen. Results also showed that N-linked giycosy lation was not responsible for the charge heterogeneity of the 1D4 antigen. The oligosaccharide chain-related epitope was detected in rat brain but not in mouse, rabbit, or bovine brain, but the 1D4 antigen was recognized in rat and mouse brains with antiserum (polyclonal antibodies). These findings indicate that the oligosaccharide-related epitope is species specific. Furthermore, results with neuraminidase-treated 1D4 antigen indicated that sialic acids were not involved in the oligosaccharide-related epitope. These findings suggest that the 1D4 antigen may have the oligosaccharide structure specific for rat brain and itself.
    Type of Medium: Electronic Resource
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  • 95
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The intracellular nonmitochondrial calcium pools of saponin-permeabilized NG108–15 cells were characterized using inositol 1,4,5-trisphosphate (IP3) and GTP. IP3 or GTP alone induced release of 47 and 68%, respectively, of the calcium that was releasable by A23187. GTP induced release of a further 24% of the calcium after IP3 treatment, whereas IP3 induced release of a further 11 % of the calcium after GTP treatment. Guanosine 5′-O-(3-thio)triphosphate had little effect on IP3-induced calcium release but completely inhibited GTP-induced calcium release. In contrast, heparin inhibited the action of IP3 but not that of GTP. The results imply the existence of at least three nonmitochondrial pools: (a) 31% is releasable by IP3 and GTP, (b) 11% is releasable by IP3 alone, and (c) 24% is releasable by GTP alone. GTP enhanced calcium uptake in the presence of oxalate with an EC50 of 0.6 μM and stimulated calcium release in the absence of oxalate with an EC50 of 0.32 μM. The similar EC50 values for these dual effects of GTP on calcium movement suggest that GTP exerts its dual action by the same mechanism.
    Type of Medium: Electronic Resource
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  • 96
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The receptors mediating the inhibition of D1 dopamine receptor-stimulated adenylate cyclase by opioids were examined in primary cultures of rat neostriatal neurons. Adenylate cyclase activity was dose-dependently increased by the selective D1 dopamine receptor agonist SKF 38393 (EC50= 0.05 μM). This stimulation was fully antagonized by the selective D1 dopamine receptor antagonist SCH 23390 (1 μM). SKF 38393 (1 μM)-stimulated adenylate cyclase activity was strongly reduced (by almost 60%) by the highly selective μ-agonist [D-Ala2,MePhe4,Gly-ol5]-enkephalin (DAGO; EC50= 0.006μM) and high concentrations of the selective δ-agonist [d-Ser2(O-tert-butyl), Leu5]-enkephaIyl-Thr6 (DSTBU-LET; EC50= 0.13 μM) but not by the selective δ-agonist [d-penicillamine2, d-penicillamine5]enkephalin (DPDPE). D1 dopamine receptor-stimulated adenylate cyclase activity was also slightly reduced (by ∼20%) by high concentrations of the k-agonist U50,488 (EC50= 0.63 μM). The inhibitory effects of submaximally effective concentrations of DAGO, DSTBULET, and U50,488 were equally well antagonized by the μ-opioid receptor-selective antagonist naloxone (EC50 of ∼0.1 μM). Neither the irreversible δ-ligand fentanyl isothiocyanate (1 μM) nor the reversible δ-antagonist ICI 174864 (1 μM) reversed the inhibitory effects of DSTBULET. The inhibitory effects of DAGO and U50,488 were equally well reversed by high concentrations (〉0.1 μM) of the k-opioid receptor-selective antagonist norbinaltorphimine. The effect of DAGO (1 μM) was already detectable after 1 day in culture, whereas DPDPE (1 μM) had no effect even after 28 days in culture. These data indicate that an homogeneous population of μ-opioid receptors coupled as inhibitors to D1 dopamine receptor-stimulated adenylate cyclase is expressed in rat neostriatal neurons in primary culture.
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  • 97
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cyclic AMP levels in rabbit carotid bodies incubated under control conditions, 100% O2- or 95% O2/5% CO2-equilibrated medium, are close to 1 pmol/mg wet tissue (range 0.4–2.43 pmol/mg). Isobutylmethylxanthine (0.5 mM) increases cyclic AMP levels by a factor of 14 and 8 in HEPES-and CO2/CH3O−-buffered medium, respectively. Forskolin (0.5–10 μM) applied during 30 min increases cyclic AMP levels in a dose-dependent manner. Incubation of carotid bodies at low O2 tensions resulted in an elevation of cyclic AMP levels both in the absence and in the presence of isobutylmethylxanthine. In the latter conditions cyclic AMP increase was maximum at an O2 tension of 46 mm Hg and tended to decrease at extremely low Po2. In isobutylmethylxanthine-containing Ca2+-free medium, cyclic AMP increased linearly with decreasing Po2 from 66 to 13 mm Hg; the absolute cyclic AMP levels attained in Ca2+-free medium were smaller than those observed in Ca2+-containing medium at any Po2. The differences between Ca2+-free and Ca2+-containing media appear to be due to the action of released neurotransmitters in the latter conditions, because dopamine and norepinephrine, which are known to be released by hypoxia in a Ca2+-dependent manner, increase cyclic AMP in the carotid body. Low pH/high Pco2 and high [K+]e increase cyclic AMP levels only in Ca2+-containing medium. Forskolin potentiates the release of catecholamines induced by low Po2. These results suggest that cyclic AMP plays an important role in the modulation of the chemoreception process.
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  • 98
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cyclic AMP accumulation in brain slices incubated with adenosine or the adenosine analogue 2-chloroadenosine was examined in different areas of rat cerebral cortex following a unilateral injection of FeCl2 solution into the sensorimotor cortex to induce chronic epileptic activity. In the epileptic cortex, cyclic AMP accumulation in cortical slices was elicited three- to 11-fold by adenosine. The elicitation by adenosine of cyclic AMP accumulation was markedly inhibited by the adenosine antagonist 8-phenyltheophylline. In anterior cortical areas of rats in which the appearance of electrographic isolated spikes was dominant either ipsilateral or contralateral to the injection site 8 days or more after the injection, the adenosine-elicited accumulation of cyclic AMP was greater on the side of dominant spike activity than on the other. In anterior cortical areas of rats showing nearly equal spike activity on the two sides 19 days or more after the injection, the cyclic AMP accumulation was greater on the side ipsilateral to the injection site than on the other. In anterior and posterior cortical areas of rats showing spike-and-wave complexes and isolated spikes 1 month or more after the injection, the cyclic AMP accumulation was greater on the ipsilateral side than on the other. Similar regional differences in the adenosine-elicited accumulation of cyclic AMP were detected in the presence of the adenosine uptake inhibitor dipyridamole or the phosphodiesterase inhibitor dl-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20–1724). The cyclic AMP accumulation was elicited five- to 17-fold by 2-chloroadenosine, in which case the elicitation was markedly inhibited by 8-phenyltheophylline. Regional differences in the 2-chloroadenosine-elicited accumulation of cyclic AMP were similar to those with adenosine and were detected in the presence of Ro 20–1724 or adenosine deaminase. The regional differences which correlated with the electrographic discharge patterns were due mainly to persistent changes in cyclic AMP accumulation on the primary epileptic side. These results suggest that alterations in adenosine-sensitive cyclic AMP generation in the cortex are associated with the neurochemical process leading to chronic iron-induced epilepsy.
    Type of Medium: Electronic Resource
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  • 99
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A lipid extract with a composition similar to that of myelin was used to prepare liposomes and proteoliposomes containing the Folch-Lees proteolipid apoprotein. Freeze-fracture replicas of the proteoliposomes were prepared to demonstrate the presence of intramembrane protein particles in the fracture faces of the lipid bilayer. Experiments with 45CaCl2 showed that a steady calcium movement occurs across liposomal membranes, approaching equilibrium between intra- and extravesicular spaces. The most significant finding was that Mg-ATP, ATP analogues, and other nucleotides depressed significantly the calcium fluxes in proteoliposomes, having no effect on liposomes that lacked the proteolipid protein. It is suggested that this intrinsic protein, interacting with nucleotides and endogenous lipids, could be involved in the regulation of calcium levels in myelin by means of a conformational change mechanism. These observations could lead to implications concerning the pathophysiology of myelin.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The temperature dependence of in vitro binding of [3H]Ro 15–1788 to benzodiazepine receptors in human postmortem neocortex and neocerebellum homogenates was studied. An increase of the equilibrium dissociation constants (KD) from 1.40 nmol/L and 1.04 nmol/L at 4°C to 6.10 nmol/L and 8.91 nmol/L at 37°C was found for neocortex and neocerebellum, respectively. In contrast, maximal binding (Bmax) remained in the range of 30–35 fmol/mg for neocortex and 24–27 fmol/mg of tissue (wet weight) for neocerebellum at all the temperatures. The KD of 6.10 nmol/L for neocortex at 37°C in vitro is of the same order as the KD of 10 nmol/L obtained by positron emission tomography for [11C]Ro 15–1788 binding to benzodiazepine receptors in the human neocortex in vivo. The differences in KD between in vitro and in vivo benzodiazepine receptor binding to human neocortex and cerebellum seem to be due at least partially to temperature differences of in vitro and in vivo studies.
    Type of Medium: Electronic Resource
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