DOI: 10.1002/ana.410110406. Measurement of the scrapie agent using an incubation time interval assay

Measurement of the scrapie agent using an incubation time interval assay

10.1002/ana.410110406

Crossref journal-article

Wiley

Annals of Neurology (311)

Abstract

AbstractThe titer of the scrapie agent was determined by measurements of time intervals from inoculation to onset of illness and from inoculation to death. Both intervals were found to be inversely proportional to the size of the dose injected intracerebrally into random‐bred weanling Syrian hamsters. The logarithms of the time intervals minus a time factor were linear functions of the logarithm of the inoculum size. The time factors were determined by regression analysis in order to maximize these linear relationships. An equation relating the titer of the inoculum to the dilution of the sample and the length of the time intervals was developed. This equation facilitates the use of a computerized data base. Validation of these relationships was provided by comparing samples for which the agent was measured both by end‐point titration and by time interval assay. Agreement between the two methods was generally within ±0.5 log10 median infective dose units. No differences between the molecular properties of the agents from hamster and murine sources were observed using primarily the incubation time interval method with the former and end‐point titration with the latter. The advantages of this new approach based on time interval measurements are considerable with respect to time and resources.

Bibliography

Prusiner, S. B., Cochran, S. P., Groth, D. F., Downey, D. E., Bowman, K. A., & Martinez, H. M. (1982). Measurement of the scrapie agent using an incubation time interval assay. Annals of Neurology, 11(4), 353â358. Portico.

Authors 6

Stanley B. Prusiner (first)
S. Patricia Cochran (additional)
Darlene F. Groth (additional)
Deborah E. Downey (additional)
Karen A. Bowman (additional)
Hugo M. Martinez (additional)

References 32 Referenced 280

{'key': 'e_1_2_1_2_2', 'first-page': '843', 'article-title': 'Biological studies on the Rous sarcoma virus. IV. Interpretation of tumor‐response data involving one inoculation site per chicken', 'volume': '16', 'author': 'Bryan WR', 'year': '1956', 'journal-title': 'Natl Cancer Inst J'} / Natl Cancer Inst J / Biological studies on the Rous sarcoma virus. IV. Interpretation of tumor‐response data involving one inoculation site per chicken by Bryan WR (1956)
10.1111/j.1749-6632.1957.tb49710.x
10.1093/infdis/65.3.306
10.4049/jimmunol.73.1.1 / J Immunol / The number of elementary bodies per 50% lethal dose of meningo‐pneumonitis virus as determined by electron microscopic counting by Crocker TT (1954)
10.1016/0021-9975(69)90021-8
{'key': 'e_1_2_1_7_2', 'first-page': '169', 'volume-title': 'Techniques in Experimental Virology', 'author': 'Dougherty R', 'year': '1964'} / Techniques in Experimental Virology by Dougherty R (1964)
{'key': 'e_1_2_1_8_2', 'first-page': '1055', 'article-title': 'Dose‐response relations in experimental transmission of avian erythromyeloblastic leukosis. III. Titration of the virus', 'volume': '14', 'author': 'Eckert EA', 'year': '1954', 'journal-title': 'Natl Cancer Inst J'} / Natl Cancer Inst J / Dose‐response relations in experimental transmission of avian erythromyeloblastic leukosis. III. Titration of the virus by Eckert EA (1954)
10.3181/00379727-112-28225
10.1126/science.142303
10.1084/jem.72.1.69
10.1093/infdis/138.3.396
10.4049/jimmunol.120.6.1986 / J Immunol / Supression of polyclonal B cell activation in scrapie‐infected C3H/HeJ mice by Garfin DE (1978)
10.1093/infdis/92.3.240
10.4049/jimmunol.59.1.71 / J Immunol / A single‐dilution method for the estimation of LD50 titers of the psittacosis‐LGV group of viruses in chick embryos by Golob OJ (1948)
10.1002/ana.410080615
{'key': 'e_1_2_1_17_2', 'first-page': '34', 'article-title': 'Progressive retinal degeneration in scrapie‐infected hamsters: a light and electron microscopic analysis', 'volume': '44', 'author': 'Hogan RN', 'year': '1981', 'journal-title': 'Lab Invest'} / Lab Invest / Progressive retinal degeneration in scrapie‐infected hamsters: a light and electron microscopic analysis by Hogan RN (1981)
10.1099/0022-1317-34-2-295
10.1016/0021-9975(79)90046-X
{'key': 'e_1_2_1_20_2', 'first-page': '35', 'volume-title': 'General Virology', 'author': 'Luria SE', 'year': '1967'} / General Virology by Luria SE (1967)
{'key': 'e_1_2_1_21_2', 'first-page': '2076', 'article-title': 'The Syrian hamster as a model for the study of slow virus diseases caused by unconventional agents', 'volume': '37', 'author': 'Marsh RF', 'year': '1977', 'journal-title': 'Fed Proc'} / Fed Proc / The Syrian hamster as a model for the study of slow virus diseases caused by unconventional agents by Marsh RF (1977)
10.1093/infdis/131.2.104
10.1016/S0368-1742(61)80040-4
{'key': 'e_1_2_1_24_2', 'first-page': '73', 'volume-title': 'Neurochemistry and Clinical Neurology', 'author': 'Prusiner SB', 'year': '1980'} / Neurochemistry and Clinical Neurology by Prusiner SB (1980)
{'key': 'e_1_2_1_25_2', 'first-page': '205', 'volume-title': 'Aging of the Brain and Dementia', 'author': 'Prusiner SB', 'year': '1980'} / Aging of the Brain and Dementia by Prusiner SB (1980)
{'key': 'e_1_2_1_26_2', 'first-page': '425', 'volume-title': 'Slow Transmissible Diseases of the Nervous System', 'author': 'Prusiner SB', 'year': '1979'} / Slow Transmissible Diseases of the Nervous System by Prusiner SB (1979)
10.1111/j.1471-4159.1980.tb03693.x
10.1073/pnas.77.5.2984
10.1021/bi00562a028
10.1021/bi00616a020
10.1021/bi00616a021
10.1073/pnas.78.11.6675
10.1016/S0007-1935(17)50172-4

Dates

Type	When
Created	20 years, 7 months ago (Jan. 1, 2005, 8:30 a.m.)
Deposited	1 year, 9 months ago (Nov. 2, 2023, 1:16 p.m.)
Indexed	2 weeks, 5 days ago (Aug. 7, 2025, 4:57 p.m.)
Issued	43 years, 4 months ago (April 1, 1982)
Published	43 years, 4 months ago (April 1, 1982)
Published Online	20 years, 10 months ago (Oct. 7, 2004)
Published Print	43 years, 4 months ago (April 1, 1982)

Funders 0

None

BibTeX

@article{Prusiner_1982, title={Measurement of the scrapie agent using an incubation time interval assay}, volume={11}, ISSN={1531-8249}, url={http://dx.doi.org/10.1002/ana.410110406}, DOI={10.1002/ana.410110406}, number={4}, journal={Annals of Neurology}, publisher={Wiley}, author={Prusiner, Stanley B. and Cochran, S. Patricia and Groth, Darlene F. and Downey, Deborah E. and Bowman, Karen A. and Martinez, Hugo M.}, year={1982}, month=apr, pages={353–358} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        7
      ]
    ],
    "date-time": "2025-08-07T20:57:08Z",
    "timestamp": 1754600228032
  },
  "reference-count": 32,
  "publisher": "Wiley",
  "issue": "4",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2004,
            10,
            7
          ]
        ],
        "date-time": "2004-10-07T00:00:00Z",
        "timestamp": 1097107200000
      },
      "content-version": "vor",
      "delay-in-days": 8225,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1982,
        4
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>The titer of the scrapie agent was determined by measurements of time intervals from inoculation to onset of illness and from inoculation to death. Both intervals were found to be inversely proportional to the size of the dose injected intracerebrally into random\u2010bred weanling Syrian hamsters. The logarithms of the time intervals minus a time factor were linear functions of the logarithm of the inoculum size. The time factors were determined by regression analysis in order to maximize these linear relationships. An equation relating the titer of the inoculum to the dilution of the sample and the length of the time intervals was developed. This equation facilitates the use of a computerized data base. Validation of these relationships was provided by comparing samples for which the agent was measured both by end\u2010point titration and by time interval assay. Agreement between the two methods was generally within \u00b10.5 log<jats:sub>10</jats:sub> median infective dose units. No differences between the molecular properties of the agents from hamster and murine sources were observed using primarily the incubation time interval method with the former and end\u2010point titration with the latter. The advantages of this new approach based on time interval measurements are considerable with respect to time and resources.</jats:p>",
  "DOI": "10.1002/ana.410110406",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        1,
        1
      ]
    ],
    "date-time": "2005-01-01T13:30:35Z",
    "timestamp": 1104586235000
  },
  "page": "353-358",
  "source": "Crossref",
  "is-referenced-by-count": 280,
  "title": "Measurement of the scrapie agent using an incubation time interval assay",
  "prefix": "10.1002",
  "volume": "11",
  "author": [
    {
      "given": "Stanley B.",
      "family": "Prusiner",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "S. Patricia",
      "family": "Cochran",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Darlene F.",
      "family": "Groth",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Deborah E.",
      "family": "Downey",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Karen A.",
      "family": "Bowman",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Hugo M.",
      "family": "Martinez",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2004,
        10,
        7
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_1_2_2",
      "first-page": "843",
      "article-title": "Biological studies on the Rous sarcoma virus. IV. Interpretation of tumor\u2010response data involving one inoculation site per chicken",
      "volume": "16",
      "author": "Bryan WR",
      "year": "1956",
      "journal-title": "Natl Cancer Inst J"
    },
    {
      "key": "e_1_2_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1749-6632.1957.tb49710.x"
    },
    {
      "key": "e_1_2_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/infdis/65.3.306"
    },
    {
      "key": "e_1_2_1_5_2",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.4049/jimmunol.73.1.1",
      "article-title": "The number of elementary bodies per 50% lethal dose of meningo\u2010pneumonitis virus as determined by electron microscopic counting",
      "volume": "73",
      "author": "Crocker TT",
      "year": "1954",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_2_1_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0021-9975(69)90021-8"
    },
    {
      "key": "e_1_2_1_7_2",
      "first-page": "169",
      "volume-title": "Techniques in Experimental Virology",
      "author": "Dougherty R",
      "year": "1964"
    },
    {
      "key": "e_1_2_1_8_2",
      "first-page": "1055",
      "article-title": "Dose\u2010response relations in experimental transmission of avian erythromyeloblastic leukosis. III. Titration of the virus",
      "volume": "14",
      "author": "Eckert EA",
      "year": "1954",
      "journal-title": "Natl Cancer Inst J"
    },
    {
      "key": "e_1_2_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.3181/00379727-112-28225"
    },
    {
      "key": "e_1_2_1_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.142303"
    },
    {
      "key": "e_1_2_1_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.72.1.69"
    },
    {
      "key": "e_1_2_1_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/infdis/138.3.396"
    },
    {
      "key": "e_1_2_1_13_2",
      "doi-asserted-by": "crossref",
      "first-page": "1986",
      "DOI": "10.4049/jimmunol.120.6.1986",
      "article-title": "Supression of polyclonal B cell activation in scrapie\u2010infected C3H/HeJ mice",
      "volume": "120",
      "author": "Garfin DE",
      "year": "1978",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_2_1_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/infdis/92.3.240"
    },
    {
      "key": "e_1_2_1_15_2",
      "doi-asserted-by": "crossref",
      "first-page": "71",
      "DOI": "10.4049/jimmunol.59.1.71",
      "article-title": "A single\u2010dilution method for the estimation of LD50 titers of the psittacosis\u2010LGV group of viruses in chick embryos",
      "volume": "59",
      "author": "Golob OJ",
      "year": "1948",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_2_1_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/ana.410080615"
    },
    {
      "key": "e_1_2_1_17_2",
      "first-page": "34",
      "article-title": "Progressive retinal degeneration in scrapie\u2010infected hamsters: a light and electron microscopic analysis",
      "volume": "44",
      "author": "Hogan RN",
      "year": "1981",
      "journal-title": "Lab Invest"
    },
    {
      "key": "e_1_2_1_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1099/0022-1317-34-2-295"
    },
    {
      "key": "e_1_2_1_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0021-9975(79)90046-X"
    },
    {
      "key": "e_1_2_1_20_2",
      "first-page": "35",
      "volume-title": "General Virology",
      "author": "Luria SE",
      "year": "1967"
    },
    {
      "key": "e_1_2_1_21_2",
      "first-page": "2076",
      "article-title": "The Syrian hamster as a model for the study of slow virus diseases caused by unconventional agents",
      "volume": "37",
      "author": "Marsh RF",
      "year": "1977",
      "journal-title": "Fed Proc"
    },
    {
      "key": "e_1_2_1_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/infdis/131.2.104"
    },
    {
      "key": "e_1_2_1_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0368-1742(61)80040-4"
    },
    {
      "key": "e_1_2_1_24_2",
      "first-page": "73",
      "volume-title": "Neurochemistry and Clinical Neurology",
      "author": "Prusiner SB",
      "year": "1980"
    },
    {
      "key": "e_1_2_1_25_2",
      "first-page": "205",
      "volume-title": "Aging of the Brain and Dementia",
      "author": "Prusiner SB",
      "year": "1980"
    },
    {
      "key": "e_1_2_1_26_2",
      "first-page": "425",
      "volume-title": "Slow Transmissible Diseases of the Nervous System",
      "author": "Prusiner SB",
      "year": "1979"
    },
    {
      "key": "e_1_2_1_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1471-4159.1980.tb03693.x"
    },
    {
      "key": "e_1_2_1_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.77.5.2984"
    },
    {
      "key": "e_1_2_1_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00562a028"
    },
    {
      "key": "e_1_2_1_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00616a020"
    },
    {
      "key": "e_1_2_1_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00616a021"
    },
    {
      "key": "e_1_2_1_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.78.11.6675"
    },
    {
      "key": "e_1_2_1_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0007-1935(17)50172-4"
    }
  ],
  "container-title": "Annals of Neurology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fana.410110406",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.410110406",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        11,
        2
      ]
    ],
    "date-time": "2023-11-02T17:16:50Z",
    "timestamp": 1698945410000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1002/ana.410110406"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1982,
        4
      ]
    ]
  },
  "references-count": 32,
  "journal-issue": {
    "issue": "4",
    "published-print": {
      "date-parts": [
        [
          1982,
          4
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1002/ana.410110406"
  ],
  "URL": "http://dx.doi.org/10.1002/ana.410110406",
  "relation": {},
  "ISSN": [
    "0364-5134",
    "1531-8249"
  ],
  "subject": [],
  "container-title-short": "Annals of Neurology",
  "published": {
    "date-parts": [
      [
        1982,
        4
      ]
    ]
  }
}