ULTRASTRUCTURE OF THE LACTIC DEHYDROGENASE VIRUS (LDV) AND CELL-VIRUS RELATIONSHIPS.
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Biomedical subjects
Publications and source records attributed to A L NOTKINS.
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The procedure used to determine the infective titer of the LDH agent, the reproducibility of this assay, and the relationship between virus dose and plasma enzyme activity were described. Multiplication of the LDH agent began within 6 hours after infection and reached 10(10.8) ID(50)/ml of plasma within 24 hours. The titer rapidly decreased over the next 72 hours but viremia persisted for at least 16 months with titers as high as 10(5.2) ID(50)/ml. The appearance of the LDH agent in the circulation preceded the first noticeable rise in plasma LDH activity by close to 24 hours. After 10 months, when the plasma titer of the LDH agent had decreased nearly one millionfold, the plasma enzyme LDH had decreased by less than 50 per cent. The LDH agent is inactivated by ether but withstands lyophilization, and freezing and thawing. It is stable at low temperatures. Ultracentrifugation at 105,000 G for 2 hours leaves less than 0.1 per cent of the LDH agent in the supernatant fluid and filtration through gradocol membranes suggesst that the upper size of the LDH agent is about 55 mmicro. Spread of the LDH agent from infected to uninfected mice kept in the same cage and transmission from mothers (infected prior to mating) to their offspring was relatively low.
Within 72 hours after injection of the LDH agent into normal mice, five (LDH, ICDH, MDH, PHI, and GOT) out of the seven plasma enzymes studied were elevated. This elevation persisted for the duration of the experiment. Alkaline phosphatase and aldolase were not elevated. Plasma from mice bearing tumor SS-70429 and infected with the LDH agent showed 7 times more LDH, 8 times more ICDH, and 4 times more MDH activity than the plasma from mice with the same tumor but uninfected. The plasma aldolase activity from the infected tumor-bearing animal was approximately the same as that from the uninfected tumor-bearing animal. Somewhat similar results, but lower in magnitude, were found with mice bearing mammary carcinoma C(3)HBA. The early rise in plasma enzyme activity (LDH, MDH, ICDH) prior to the actual appearance of the tumor was shown to be due not to the tumor, but to the LDH agent. Uninfected tumor-bearing mice showed a late increase in plasma enzyme activity which appeared to be related to tumor growth. The findings reported above suggest that contamination with the LDH agent may have been responsible for much of the increased plasma enzyme activity previously attributed to the tumor.
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The lactic dehydrogenase agent (LDH agent) was found in the urine, feces, and saliva of mice within 24 hours after inoculation. The titer of virus in these materials appears to be directly related to the titer in the plasma. Infection by the oral route occurred only when a high concentration of virus was used. Animals infected prior to mating rarely transmitted the LDH agent to their progeny. However, 91.2 per cent of the progeny of mothers infected during gestation and 51.5 per cent of the progeny of mothers infected within 48 hours after giving birth became infected with the LDH agent. Evidence is discussed which suggests that the transmission of the LDH agent from the infected mother to her offspring is related to the titer of the LDH agent in the maternal circulation.
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