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Biomedical subjects

F T Valentine

Publications and source records attributed to F T Valentine.

36 records · Page 2Linked to original sources
PubMed1979

The proliferative response of human lymphocytes to antigen is suppressed preferentially by lymphocytes precultured with the same antigen.

Human blood lymphocytes activated in vitro with antigen to which the donor is reactive are capable of suppressing the secondary proliferative response of autochthonous fresh cells to antigen. Both antigen-specific and antigen-nonspecific suppression can be detected in each experiment. These suppressor cells act by decreasing the number of lymphocytes entering the proliferative response rather than by slowing or otherwise inhibiting ongoing proliferation. The suppressor cells must be added soon after fresh cells are stimulated with antigen to be effective, but the suppressor cells themselves need not proliferate to exert their effect. Suppressor cells are optimally effective when added in numbers equal to those of the responding population, but still exert a significant effect at one-eighth that number.

Antigens↗
PubMed1976

Requirement of precommitted cells as targets for the augmentation of lymphocyte proliferation by leukocyte dialysates.

After our initial report tha leukocyte dialysates containing transfer factor augment the thymidine incorporation of antigen-stimulated lymphocytes, we have adapted the system to microleukocyte cultures. This modification permits both (a) the simultaneous assay of a single dialysate on the cells of multiple individuals, and (b) the assay of multiple dialysates on the cells of a single individual. The data thus secured, demonstrate that dialysates from both skin-test-positive and -negative donors produced similar degrees of augmentation whether the data are expressed as an arithmetic difference or as a ratio. When expressed as an arithmetic difference, the amount of augmentation is increased in proportion to the level of thymidine incorporation of the assay cells when they were stimulated by antigen alone. When expressed as a ratio, however, the degree of augmentation is independent of the response of the assay cells. An analysis of the ability of dialysates to engage previously uncommitted lymphocytes and thus to augment thymidine incorporation, revealed that precommitted cells were required. In these experiments, antigen-reactive cells were deleted from populations of peripheral blood lymphocytes by incubation with purified protein derivative of tuberculin, diphtheria toxoid, or streptokinase-streptodornase in the presence of [3H]thymidine of high specific activity. This deletion depressed or abolished the effect of dialysate on the residual population when it was recultured with the same antigen, but the effect on the response of the remaining lymphocytes to other antigens was unaltered. In this study, leukocyte dialysate appeared to augment nonspecifically the thymidine incorporation of an antigen-specific precommitted clone of lymphocytes. The relationship of these adjuvant effects on peripheral blood lymphocytes in vitro to the specific and nonspecific activities of transfer factor in vivo remains to be elucidated.

Adjuvants, Immunologic↗
PubMed1976

A micromethod for evaluating the phagocytic activity of human macrophages by ingestion of radio-labelled polystyrene particles.

Studies in vitro of human macrophage function in health and disease have been impeded by the difficulty of obtaining such cells in sufficient number. Unlike animal species, the only readily available source of human macrophages are circulating monocytes. Herein, a method is described whereby the phagocytic rate of small numbers of glass-adherent mononuclear cells can be accurately measured. The method utilizes the ingestion by macrophages of technetium labelled polystyrene particles; both the radiolabel and ingestible substrate are readily available and the labelling process simple and efficient. The phagocytic rate can be expressed as radioactive counts per microgram of cell protein; data is also presented showing that the number of particles ingested per cell can be accurately derived.

Blood Cell Count↗
PubMed1974

In vitro properties of leukocyte dialysates containing transfer factor.

The chief impediment to the precise biochemical identification of transfer factor and its mechanism of action has been the lack of a reproducible in vitro assay. We now report on a method by which dialysates containing transfer factor of proven in vivo potency can convert nonimmune lymphocytes to immune responsiveness in vitro, as reflected by antigen-triggered lymphocyte proliferation. However, "water-dialyzed transfer factor" (TF(D)) prepared for in vivo use by the conventional method of dialysis against large volumes of water exhibits diminished activity in vitro and is frequently toxic to lymphocyte cultures. This problem can be avoided by dialysis of transfer factor into tissue culture medium. When this precaution is taken, such "media-dialyzed transfer factor" (TF(DM)) causes nonimmune lymphocytes to respond to antigen by an increment of thymidine incorporation that ranges from 2 to 25 times that of such cells cultured with antigen alone. This response is generally observed only in the presence of those antigens to which the TF(DM) donor expresses delayed cutaneous reactivity and is distinguishable from nonspecific adjuvant effects.

Adjuvants, Immunologic↗
PubMed1974

Effects of dialyzable transfer factor in patients with breast cancer.

Five patients with advanced breast cancer were treated with pooled dialyzable transfer factor from healthy adult donors. The period of treatment ranged from 21 to 310 days, the total dose from 20 to 257 ml. Transfer factor did not elicit inflammatory or hypersensitivity reactions or detectable formation of antibody to itself, nor any hematological or biochemical abnormalities or other side effects. Three patients became responsive (by skin test) to tuberculin and/or streptococcal antigens. Marked partial regression of the breast cancer, lasting 6 months, was observed in one patient.

Adult↗
PubMed1969

Cellular immunity in vitro. Clonal proliferation of antigen-stimulated lymphocytes.

When sensitive lymphocytes are cultured with the appropriate antigen, lymphoblasts appear after 24-48 hr of incubation and the number of these increases steadily from the 2nd to the 6th or 7th day. Our problem was to discover, at a cellular level, how this increase takes place; whether it is a massive response of many cells, stepwise recruitment of cells into the lymphoblast class, or simply repeated division of a few cells to form clones. In these experiments lymphocytes were incubated with antigen in culture tubes for 2-4 days and then a few cells, usually less than 200, were transferred to special microchambers for further culture. In these microchambers the cells could be viewed continually with a microscope and their fate recorded over the next 3-5 days by time-lapse cinemicrography. Examination of the film produced in this way showed that lymphoblasts divided and redivided to produce clones of 64 cells or more. It was possible to measure generation times from the film for 301 cells; the majority were between 8 and 13 hr but the range was 7.5-38.0 hr. There was no clear difference between generation times of human lymphocytes stimulated with tuberculin, streptokinase-streptodrnase, extract of the American pokeweed, or in the mixed leukocyte reaction. Similar times were also found for rat cells in the mixed leukocyte reaction. While these observations show that clonal proliferation does occur and could reasonably account for all the increase of lymphoblasts in lymphocyte cultures, the experiments, because of their design, do not exclude the possibility that other mechanisms such as recruitment may play a role as well, particularly during the first 48 hr after contact between sensitive cells and antigens.

Animals↗
PubMedDate not supplied

Phase I study of 2',3'-dideoxyinosine: experience with 19 patients at New York University Medical Center.

We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine (didanosine; ddI) in 19 patients with AIDS or AIDS-related complex in order (1) to establish the maximal tolerated dosage, (2) to determine the nature of toxic adverse effects, (3) to measure changes in levels of circulating human immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate the pharmacokinetics of ddI. Almost all patients had received zidovudine therapy previously. The maximal tolerated dosage of ddI was found to be approximately 12 mg/(kg.d) when it was administered orally for 28 weeks. The major dosage-limiting adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These occurred at dosages higher than those associated with decreases in levels of p24 antigen. The major toxic effects of ddI are different from those associated with zidovudine. At the proper dosage, ddI may prove to be an effective agent for the chronic treatment of infection with human immunodeficiency virus and should be especially useful in the treatment of patients who cannot tolerate zidovudine.

AIDS-Related Complex↗