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Biomedical subjects

S S Lefkowitz

Publications and source records attributed to S S Lefkowitz.

At least 55 records · Page 3Linked to original sources

Properties of bovine interferons.

This study was done in an attempt to elucidate some of the properties of bovine IFNs. Maximum levels of both fibroblast and leukocyte IFNs occurred prior to 24 h whereas maximum levels of immune IFN were not reached until after 72 h. The latter species of IFN was unstable at either pH 2 or 56 degrees C whereas both the fibroblast and leukocyte IFNs were more stable under these conditions. Studies of cross-species protection between fibroblast and leukocyte IFNs indicate that the former was more protective for other species than the latter.

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Interferon production following NO2 exposure.

Studies were undertaken to assess the effects of nitrogen dioxide (NO2) on interferon (IFN) production in mice. Mice were exposed to either 5.0 ppm for 7 days or 25 ppm for 3 days followed by an i.p. injection with the IFN inducer, polyinosinic-polycytidilic acid (poly I:C). Sera and organ homogenates made from spleens and lungs were assayed for IFN. There were no significant differences in IFN levels between control and NO2 exposed mice. This was also true for isolated spleen cells from mice that were exposed in vitro to poly I:C. Under the conditions employed, it can be concluded that NO2 did not alter IFN production.

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Priming of bovine interferons.

Bovine interferons (IFNs) were able to prime either bovine leukocytes or bovine kidney (MDBK) cells, greatly enhancing the production of IFNs. The priming could be readily demonstrated by leukocyte, fibroblast, and immune IFNs. Differences between the priming abilities of the various IFNs remain to be evaluated.

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Priming of L cells by murine immune interferon.

Partially purified murine immune interferon (IFN gamma) was found to be equivalent to IFN alpha/beta in its ability to enhance the production of IFN alpha/beta by L-929 cells. While crude preparations were also able to prime, it was apparent that such preparations of IFN contained 'blocking factors' that reduced the priming efficiency of IFN. Exposing IFN gamma to heat, low pH or its specific antibody readily destroyed its ability to prime, providing evidence that IFN gamma itself was responsible for priming.

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Antiviral action of murine interferons on heterologous cells.

Five murine interferon preparations wer compared for their antiviral action on 10 heterologous cell types. Immune interferon preparations induced by either BCG/ old tuberculin in vivo or concanavalin A in vitro exhibited some protection on porcine, monkey and rat cells. This was also noted with interferon induced by polyriboinosinic acid: polyribocytidylic acid (poly I:C) in spleen cells. Interferons induced by poly I:C in vivo or in L-929 cells did not protect these three cell types. All three preparations induced by poly I:C showed some activity on guinea pig cells, but this was not the case with either immune interferon preparation. None of the five preparations exhibited any measurable activity on human, bovine, chick, or rabbit cells.

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Effect of delta9-tetrahydrocannabinol on in vitro sensitization of mouse splenic lymphocytes.

The effects of delta9-tetrahydrocannabinol (delta9-THC) on the immune response of murine cells sensitized in vitro was determined using a plaque-forming cell (PFC) assay. Splenic lymphocytes from mice injected with delta9-THC showed a depressed immunologic response when compared with cells from control animals which were identically sensitized in vitro with sheep erythrocytes (SRBC). The direct addition of delta9-THC to the culture media altered the immunological response as demonstrated by a reduction in the number of PFC.

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Immunosuppression of mice by delta-9-tetrahydrocannabinol.

Studies were initiated to determine the effects of delta-9-tetrahydrocannibinol (THC) on the production of indirect IgG plaque-forming and rosette-forming cells in mice. BDF1 mice were immunized with sheep erythrocytes followed by multiple injections of 10, 25 or 40 mg/kg THC. Results indicated that both parameters were significantly reduced by 25 mg/kg, thus affirming the immunosuppressive properties of this substance in mice.

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Duration of interferon inhibition following single and multiple injections of morphine.

The increase in mouse serum interferon that occurs in response to poly I:C administration is markedly attenuated by injection of a narcotic preceding the polynucleotide challenge. A single injection of morphine is capable of inhibiting the mechanism(s) responsible for increasing serum interferon levels for a period of at least 9 days following the narcotic injection. Daily single injections of morphine for 5 or 10 days prior to poly I:C challenge do not amplify the extent of the decrease in serum interferon over that measured for a single injection, even though the amount of narcotic injected is increased on each successive day of the 5 or 10 day period. The implications of this relationship for the phenomenon of narcotic tolerance are evaluated and discussed as they relate to the immune processes.

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Role of spleen in the interferon-lowering action of morphine.

1. Polyinosinie-polycytidylic acid (Poly I:C) administered intraperitioneally to mice produced an increase in the level of interferon in the tissues of the spleen, liver, lung, and kidney. The level of circulating serum interferon also was increased by the polynucleotide. 2. The highest titer of interferon, presumably resulting from the greatest response to poly I:C was measured in the splenic tissue. 3. Morphine inhibited the poly I:C induced increase in all tissues and circulating serum. The decrease in interferon titer was similar in spleen and serum. 4. These results may indicate the serum level of interferon was more closely related and dependent upon events occuring in the spleen than in the other tissues.

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Action of naloxone on the interferon-lowering activity of morphine in the mouse.

The serum titer of interferon produced by polyinosinic:polycytidylic acid (poly I:C) was studied in mice following subcutaneous injections of either morphine alone, naloxone alone, morphine and naloxone together, morphine preceded by naloxone, naloxone preceded by morphine, or a sequence of injections of naloxone, morphine, and naloxone again. Poly I:C injected without the other drugs present served as the control. Both morphine and naloxone produced a significant decrease in the ability of the mice to increase the serum titer of interferon in response to poly I:C. Naloxone appeared to function as an antagonist to morphine when administered following the morphine injection, but not when injected before or simultaneously with the opiate. When naloxone was injected both before and following the morphine injection, results were interpreted to indicate the possibility that naloxone could function as both an agonist and antagonist under this condition.

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Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection.

The ability of ascorbic acid, sodium salicylate, and caffeine to alter the circulating serum level of interferon was investigated in mice. The animals were singly injected subcutaneously with one of the compounds, 4-8 h later again singly injected intraperitoneally with poly I:C, and bled 6-8 h afterward. The sera from the mice were assayed for interferon titer by the use of the plaque inhibition method utilizing vesicular stomatitis virus. Ascorbic acid, sodium salicylate, and caffeine increased the serum level of interferon; however, the increase produced by sodium salicylate was dose-dependent, i.e. low doses increased interferon titers, high doses decreased the titers. Caffeine produced minimal increases in the interferon titer. These observations suggest that a potential prophylactic result may occur in virus infections from administration of the three compounds either singly or in combination at the proper concentration.

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