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Biomedical subjects

F W Fitch

Publications and source records attributed to F W Fitch.

At least 181 records · Page 10Linked to original sources
PubMed1976

The production and characterization of antibodies reactive with meperidine.

Meperidinic acid was converted to O-meperidinyl-glycollic acid and covalently attached to bovine serum albumin. Rabbits injected with this conjugate produced antibodies reactive with meperidine which were measured by the ammonium sulfate method. The specificities of these antisera were studied by competitive inhibition of the binding of 100 pmol/ml of 3H-meperidine to antibody by the prior addition of increasing concentrations of various unlabeled compounds. The concentrations in nanomoles per milliliter of various unlabeled opiods required to inhibit 3H-meperidine binding by 50% (I50) were: meperidine, 0.08; O-meperidinyl-glycollic acid, 1.7; methadone, 580; heroin, 1750; codeine, 2600; and morphine, 4200. Several psychopharmacologically active compounds were found to have I50 values comparable to the nonmeperidine opioids: hydroxyzine-HC1, 460; propoxyphene, 4,500; diazepam, 6,500; and cocaine, 10,800. The metabolites of meperidine exhibited the following I50 values: normeperidine, 0.7; meperidinic acid and normeperidinic acid, 210. A radioimmunoassay for meperidine which employs this antiserum was shown to be approximately 100 times more sensitive than the spectrophotometric method of Burns et al. (J. Pharmacol. Exp. Ther. 114:289-293, 1955). In this assay only normeperidine and some of the meperidine congeners might be expected to interfere with the measurement of meperidine. The degree of normeperidine interference was shown to be comparable to that present in the existing assay method.

Animals↗
PubMed1975

The role of antibody feedback inhibition in the regulation of the secondary antibody response after high and low dose priming.

Spleen cells from mice immunized with a low dose of SRBC produce a greater secondary response to subsequent antigenic challenge in vivo than spleen cells from mice initially immunized with a larger dose. However, when the spleen cells are removed from the mice and given a secondary challange in tissue culture, a greater response is produced by cells from animals primed with the larger dose. Serum from the mice receiving the high dose of antigen contains low, but significant levels of specific antibody, and can inhibit further antibody production by lymphoid cells in vivo and in vitro. The characteristics of this suppression are similar to those known for passively administered specific antibody. Thus, antibody produced as a result of primary immunization may act through an inhibitory feedback mechanism in specifically limiting the magnitude of the secondary response to subsequent antigenic challenge in the normal animal

Animals↗
PubMed1975

Delayed clearance of morphine from the circulation of rabbits immunized with morphine-6-hemisuccinate bovine serum albumin.

Morphine clearance from the circulation of normal rabbits and rabbits with circulating anti-morphine antibody was studied. Individual animals were injected with 14C trace-labeled morphine in saline (6 mg morphine/kg body weight). The rabbits were bled at various times after morphine injection and the amount of morphine present in the serum at each time interval was determined. Morphine could be detected in the serum of normal animals for 1 week following injection and up to 12 weeks following injection in at least one animal with antibodies to morphine. The rate of morphine clearance in animals immunized to morphine-6-hemisuccinate-bovine serum albumin was not significantly different from normal during the first 4 hr after morphine injection. However, by 24 hr after injection, the rate of morphine clearance in morphine-6-hemisuccinate-bovine serum albumin-immunized animals was significantly slower than in normal animals. The amount of morphine present in the sera of the rabbits 24 hr after injection was related to the antigen-binding capacity and independent of antibody avidity. However, the rate of morphine clearance at times greater than 24 hr after injection was related to the average antibody avidity and not related to the antigen-binding capacity.

Animals↗
PubMed1975

Generation of cytotoxic T lymphocytes in vitro. VI. Effect of cell density on response in mixed leukocyte cultures.

Reexposure of day 14 murine mixed leukocyte culture (MLC) populations to the original irradiated allogeneic stimulating spleen cells has previously been found to result in the ratpid generation of cytolytic T lymphocytes (CTL) associated with a net increase in cultured cell number. Under the experimental conditions used, day 5 MLC cells appeared unable to respond to the allogeneic stimulus. In order to characterize further the development of the potential for anamnestic reactivity during the course of MLC, C57BL/6 spleen cells were incubated with irradiated (1000 rads) DBA/2 spleen cells (primary MLC) for up to 3 weeks. At various time intervals after the onset of the primary MLC, the surviving cells were collected and reexposed, at varying cell concentrations, to irradiated DBA/2 spleen cells (secondary MLC). At daily intervals thereafter, CTL activity was assessed using a quantitative 51Cr-release assay system. A paradoxic effect of responding cell concentration on generation of CTL activity was observed; relatively greater increase in CTL activity was observed as the concentration of responding cells was decreased over a 100-fold range. This effect was more pronounced with responding cells reexposed to antigen after primary MLC for 20 days, but was observed even with normal cells. The apparent unresponsiveness of day 5 MLC cells to alloantigen restimulation could be overcome by simple dilution of responding cells. Cytotoxic activity at the time of restimulation with antigen seems to be a major factor determining the magnitude of the secondary response. Since intact cells bearing alloantigens are required for the generation of CTL in MLC, residual cytotoxic cells reduce the effective antigenic stimulus by destroying stimulating cells. This effect of concentration of responding cells on generation of CTL in MLC complicates interpretation of experiments investigating the role of "inhibitor" and "helper" cell in cell-mediated immune responses occurring in vitro. Under optimal conditions, the highest CTL activity and the largest increase in total cell number was observed 4 days after restimulation of day 10 MLC cells. On a per cell basis, the lytic activity was up to 4 times greater than that observed at the peak of a primary response, and the number of viable cells recovered was nearly 20 times higher than that at the onset. Such secondary MLC are thus a convenient source of lymphoid cells selected primarily on the basis of proliferation induced by alloantigens.

Animals↗
PubMed1973

Specific suppression of immune responses.

The models we have discussed in detail demonstrate specific suppression of immune reactivity produced in normal adult animals by antibody and antigen. The mechanism of homeostasis of suppression in these models depends on continued exposure to antigen and on an active response by the host. The active response may include production of antibody directed against specific receptors as well as antibody directed against antigen. Thus, specific regulation of both antibody and cell mediated immunity to an antigen might be achieved by the use of only the biological agents of the response: antigen, antibody, and possibly antibody to receptors. The general implication is that these same biological agents are responsible for autoregulation of immune reactions occurring in nature. Presumably, these agents may be used to suppress or reverse immune responses for appropriate clinical objectives.

Animals↗