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Biomedical subjects

B Prescott

Publications and source records attributed to B Prescott.

At least 73 records · Page 4Linked to original sources

Genetic control of the antibody response to type III pneumococcal polysaccharide in mice. III. Analysis of genes governing the expression of regulatory T cell activity.

Recombinant-inbred strains of mice, as well as the progenitor strains from which they were derived, were evaluated with respect to the capacity of B cells to respond to an optimally immunogenic dose of Type III pneumococcal polysaccharide (SSS-III) and the amount of suppressor and amplifier T cell activity present. None of these functional activities was found to be linked to genes within the major histocompatibility (H-2) or the IgCH allotype complex, and several autosomal genes appeared to govern the expression of each of these characteristics.

Animals↗

Kinetics of the antibody response to type III pneumococcal polysaccharide (SSS-III). I. Use of 125I-labeled SSS-III to study serum antibody levels, as well as the distribution and excretion of antigen after immunization.

A simple method was described for the preparation of 125I-labeled type III neumococcal polysaccharide (SSS-III) with a high specific radioactivity which retained the physical and immunologic properties of native SSS-III. SSS-III was used to study the serum and tissue levels of antigen, as well as its excretion, after i.p. injection. When an optimally immunogenic dose (0.5 mug) of antigen was given, greater than 90% of the injected antigen was excreted during the first 3 days after injection; however, after day 3, the SSS-III which remained in each mouse was firmly bound to various tissues, and less than 5 ng SSS-III was released into the circulation daily. SSS-III was also used in a Farr test to measure serum antibody levels; the kinetics for the appearance of PFC/spleen and serum antibody levels were measured at 24-hr intervals after immunization with 0.5 mug of antigen. Maximum PFC/spleen were observed on day 4 after immunization whereas the peak serum antibody level was seen on day 5. The decay of serum antibody level from its maximum value was much slower than that of the PFC/spleen. The data describing the distribution of SSS-III in vivo and the measurement of serum antibody levels indicated that treadmill neutralization was not a factor in determining the serum antibody levels after immunization with an optimally immunogenic dose of SSS-III.

Animals↗

Kinetics of the antibody response to type III pneumococcal polysaccharide. II. Factors influencing the serum antibody levels after immunization with an optimally immunogenic dose of antigen.

When the number of PFC present in the spleen was measured at 24-hr intervals after immunizing with an optimally immunogenic dose of type III pneumococcal polysaccharide (SSS-III), maximal numbers of PFC were attained 4 days after immunization; thereafter, the number of PFC decreased rapidly. By contrast, serum antibody levels, which were measured in the same mice using a Farr test, reached peak values 5 days after immunization and then declined much more slowly than did the number of PFC. Two factors were found to contribute to this disparity. First, experiments conducted with splenectomized mice showed that extrasplenic antibody synthesis, which began between days 3 and 4 after immunization and peaked on days 6 to 7, accounted for nearly one-third of the total amount of serum antibody produced. Second, the average rate of antibody synthesis by PFC increased through day 6 after immunization and then declined. Antigen-antibody dissociation tests showed that the avidity of the serum antibody obtained 4 to 7 days after immunization was the same. Moreover, during the same interval, all the antibody detected by the Farr test was of the IgM class. Thus, a change in avidity or class of immunoglobulin after day 5 did not account for the disparity observed. The clearance rate of antibody injected i.v. into nonimmune and immunized mice was studied. The data obtained indicated that accelerated clearance of antibody was occurring prior to day 3 after immunization; however, after day 3 the antibody clearance rate was constant and was the same as that found when antibody was injected into nonimmune mice. These findings affirmed the results of previous studies showing that treadmill neutralization was not important in determining the serum antibody levels present after immunization with an optimally immunogenic dose of SSS-III.

Animals↗

Regulation of the antibody response to type III pneumococcal polysaccharide. V. Ontogeny of factors influencing the magnitude of the plaque-forming cell response.

Mice of different ages were evaluated with respect to their ability to give a plaque-forming cell (PFC) response to Type III pneumococcal polysaccharide (SSSIII), as well as the degree of amplifier and suppressor thymus-derived(T) cell activity present. Although the magnitude of the PFC response to an optimally immunogenic dose of SSS-III for 2-and 3-week old mice was only 7% and 14%, respectively, of that produced by adult (8-week old) mice, values comparable to those of adult animals were attained by 4 weeks of age; no significant changes in the ability to respond to SSS-III occurred thereafter. Amplifier T cell activity, which was minimal at 2 to 4 weeks of age, matured slowly and did not reach a maximum until 8 to 10 weeks of age. By contrast, suppressor T cell activity appeared to be fully developed at least as early as 2 weeks of age; here, the inhibitory effects produced could by abrogated by depletion of T cells, indicating that the unresponsiveneness induced by such cells does not result in the depletion ot irreversible inactivation of B cells capable of responding to SSS-III. These findings suggest that the inhibitory effects of suppressor T cells are predominant in young mice and that such cells may play an important role in determining the ease with which unresponsiveness is induced in neonates, and in the prevention of autoimmune disease. Also, studies conducted with adult-thymectomized mice showed that both amplifier and suppressor T cells, once seeded to the periphery, are stable and do not depend upon the presence of intact thymus for the expression or renewal of their activity.

Aging↗

Kinetics of the antibody response to type III pneumococcal polysaccharide. I. Evidence that suppressor cells function by inhibiting the recruitment and proliferation of antibody-producing cells.

For the first 126 hr after immunization of mice with an optimally immunogenic dose (0.5 mug) of Type III pneumococcal polysaccharide (SSS-III), splenic antibody-forming PFC and serum antibody levels were measured at 2- and 8-hr intervals, respectively. PFC were detected at 28 hr after immunization and then increased through 86 hr after immunization; thereafter, the number of PFC remained nearly constant for the next 20 to 24 hr, and then began to decline. In contrast, serum antibody was first detected 60 hr after immunization. The accumulation of serum antibody continued to lag behind the increase in numbers of PFC by 16 to 20 hr until maximal serum antibody levels were attained; curves fitted to the values obtained for each parameter were nearly parallel.

Animals↗

Paradoxical action of penicillin G on Staphylococcus aureus: a time study of the effect of a zonal antibiotic concentration gradient on bacterial growth.

The killing rate of a zonal concentration gradient of penicillin G on Staphylococcus aureus was studied by using a previously described triple-layer technique, enzymatic inactivation of the antibiotic, and an automatic image analyzer. This gradient determines a target image, whose center is the reservoir of antibiotic (constituted by a paper disk containing 100 U of penicillin G) and whose successive concentric zones are: a zone of slow bactericidal activity (corresponding to high levels of penicillin G), a zone of maximal bactericidal activity (corresponding to optimal levels of penicillin G), and a zone of overgrowth situated in front of the antibiotic wave.

Culture Media↗

Characterization of the lipids of mesosomal vesicles and plasma membranes from Staphylococcus aureus.

Mesosomal vesicles and plasma membranes were isolated from Staphylococcus aureus ATCC 6538P by protoplasting and differential centrifugation. The lipids of each of the two membrane fractions were extracted with pyridine-acetic acid-N-butanol, and the nonlipid contaminants were removed by Sephadex treatment. The lipids were then separated by passage through diethylaminoethyl-cellulose columns and characterized by thin-layer chromatographic, chemical, and spectral analyses. The lipids were separated into four discrete diethylaminoethyl fractions: (i) vitamin K2, carotenoids, C55 isoprenoid alcohol, and monoglucosyl diglyceride; (ii) cardiolipin, carotenoids, phosphatidyl glycerol, diglucosyl diglyceride, and an unidentified ninhydrin-positive component; (iii) cardiolipid and phosphatidyl glyderol; (iv) cardiolipin, phosphatidyl glycerol, and phosphatidyl glucose. Qualitatively, no difference in lipid composition between mesosomal vesicles and plasma membranes was found. However, based on equal dry weights of membrane materials, a relative quantitative difference in the amount of specific lipids in mesosomal vesicles and plasma membranes was observed. There are 4 times more monoglucosyl diglyceride, 2.6 times more diglucosyl diglyceride, 3.8 times more phosphatidyl glucose, 2 times more carotenoids, and 2 times more vitamin K2 found in mesosomal vesicles than in plasma membranes. The concentration of cardiolipin and phosphatidyl glycerol is 3.6 and 6 times greater, respectively, in mesosomal vesicles.

Cardiolipins↗

Thiosemicarbazones and hydrazones of alpha-methylchalkone as potential chemotherapeutic agents.

The effectiveness of chalkones and derivatives as antibacterial and antifungal agents stimulated our interest in the possibility of coupling this type of compound with certain hydrazines and thiosemicarbazides to determine the potential chemotherapeutic activity of these combinations as anticancer and antimalarial agents. Accordingly, 18 hydrazine and thiosemicarbazide derivatives of alpha-methylchalkone (dypnone) have been synthesized for study as potential antitumor agents in animal tumor systems against Walker 256 carcinosarcoma (intramuscular) and leukemia L-1210 and for antimalarial activity against Plasmodium berghei in experimentally infected mice. Of the series of chalkone derivatives, significant inhibition in preliminary tests against the Walker 256 carcinosarcoma (intramuscular) rat tumor system was exhibited by alpha-methylchalkone-1,4-phthalazinediyldihydrazone and showed activity in the leukemia 1210 mouse tumor system. The guanylhydrazone of alpha-methylchalkone showed good inhibition with confirmed activity against Plasmodium berghei in experimentally infected mice.

Animals↗

Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. II. Relationship between IgM immunoglobulin levels and the ability to give an IgM antibody response.

Serum IgM immunoglobulin levels and antibody responses to an optimally immunogenic dose of Type III pneumococcal polysaccharide (SSS-III) were assessed for F(1), F(2), and backcross progeny derived from crosses between high responding BALB/cAnN (B) and low responding CBA/HN (C) mice. The results obtained confirmed our original hypothesis, namely, that a major component, present on the X chromosome, governs the ability to respond to SSS-III in a decisive manner. Although all low responding C mice had low IgM levels, both intermediate and high responders had high IgM levels of the same magnitude. Treatment with bacterial lipopolysaccharides (LPS) resulted in a significant increase in the IgM levels of low responding C mice. While the IgM levels attained were similar to those of high responding B mice, not given LPS, no antibody specific for LPS appeared to be produced. These findings suggest that C mice are unable to make an IgM antibody response to SSS-III and other polysaccharide antigens, despite the fact that they possess the capacity to synthesize normal amounts of IgM immunoglobulin.

Animals↗

Polyene-resistant mutants of Aspergillus fennelliae: identification of sterols.

Four mutants strains of Aspergillus fennelliae resistant to various polyene antibiotics have been analyzed for their sterol content. The mutant strains contained Delta(7,22,24(28))-ergostatrien-3beta-o1 and Delta(7,22)-ergostadien-3beta-o1 as the major sterols, whereas the wild types contained ergosterol, indicating that the mutants contain metabolic blocks for C(5)-C(6) dehydrogenation and C(24)-C(28) reduction in the biosynthesis of ergosterol. Revertant sectors arising from the mutant colonies contained either more Delta(7,22)-ergostadien-3beta-o1 than the parent mutant strain or showed the reappearance of ergosterol. The revertant sectors also showed lower resistance to amphotericin B and a higher rate of sporulation than the parent mutant strain. These results confirm our previous observations that the presence of ergosterol is directly related to the drug susceptibility and the normal rate of sporulation in this species.

Anti-Bacterial Agents↗