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Biomedical subjects

O Stutman

Publications and source records attributed to O Stutman.

At least 91 records · Page 5Linked to original sources
PubMed1979

Chemical carcinogenesis in nude mice: comparison between nude mice from homozygous matings and heterozygous matings and effect of age and carcinogen dose.

The incidence and latency periods for local tumor development after sc injection of 3-methylcholanthrene (MCA) into 30-day-old nude mice (nu/nu partially inbred on the CBA/H background) derived from homozygous matings (nu/nu times nu/nu) or heterozygous matings (nu/+ times nu/+) were comparable and did not differ with the immunologically normal controls, even when the carcinogen dosages ranged from 0.01 to 0.10 mg. Similarly, no differences in tumor incidence or latency periods between nude mice from homozygous or heterozygous matings as well as their immunologically normal controls were observed when weight-adjusted doses of MCA equivalent to 0.02 to 0.10 mg in the 30-day-old mice were administered at 120, 210, or 360 days of age. Tumor incidence was lower in nude mice and normal mice when MCA was administered at 210 and 360 days of age, especially in mice given the lower dose of MCA. The lower dosages of MCA (0.01-0.05 mg) had no detectable immunodepressive effects in normal mice. Thus the "normal" tumor incidence in nude mice after MCA administration could not be attributed to: 1) the effect of humoral thymus gland function (in the nude mice derived from heterozygous matings), 2) the immunodepressive effects of the carcinogen (the lower MCA dosages are not immunodepressive), or 3) the age of the mice at administration. These results argue against the thymus dependency of immunologic surveillance.

Age Factors↗
PubMed1978

The Qa-1 antigenic system. Relation of Qa-1 phenotypes to lymphocyte sets, mitogen responses, and immune functions.

The antiserum (B6 X A-Tlab) anti-A (Tlaa) defines several TL antigens expressed exclusively on thymocytes. When reacted with peripheral lymphocytes, the same antiserum defines another antigenic system, provisionally termed Qa-1. The genotypic disparity distinguishing the recipients and donors in this immunization comprises a section of chromosome 17 extending from a crossover point between H-2D and Tla to a presently unmarked point beyond Tla. Therefore although Qa-1 may constitute a single cell surface component, it is equally probable that the Qa-1 system defines two or more cell surface components determined by genes in this region, each of which may be expressed on a different cell set. Cytotoxicity assays indicate that Qa-1 antigen is expressed on Lyt-1 cells and Lyt-123 cells, and may serve to subclassify these two cell sets; it is not known whether Qa-1+ cells may occur within the small Lyt-23 set. There may be also be a cell set with the phenotype Thy-1--:Qa-1+. Another distinctive feature of the Qa-1 system is the characteristic profile of responses to mitogens exhibited by spleen cell populations from which Qa-1+ cells have been eliminated; in conventional assay of [3H]thymidine incorporation the response to lipopolysaccharide was essentially unchanged, the response to phytohemagglutinin M (PHA-M) was virtually abolished, and the response to concanavalin A (Con A) was reduced by 40%. The third distinctive feature of the Qa-1 system is the characteristic profile of changes which elimination of Qa-1+ cells produces in tests of immune function in vitro: (a) proliferation, measured by [3H]thymidine incorporation, in mixed lymphocyte culture (MLC) with major histocompatibility complex (MHC)-incompatible stimulator cells, was not affected. (b) in tests of cell-mediated cytotoxicity (CMC) of MHC-incompatible target cells, neither the generation nor the effector functions of cytotoxic lymphocytes was affected, implying that Lyt-23 prekiller and killer cells are Qa-1--. (c) primary and secondary responses to SRBC were considerably augmented, suggesting that Qa-1+ cells may be responsible for suppression in this test system. (d) accordingly the suppression of the anti-sheep erythrocyte (SRBC) response normally engendered in spleen cells by culture with SRBC was profoundly reduced by elimination of Qa-1+ cells, either before or after culture. (e) the suppression of the anti-SRBC response normally engendered in spleen cells cultured with Con A was reduced by removal of Qa-1+ cells before but not after culture with Con A. Although analysis is as yet far from complete, the Qa-1 system should already be of considerable value because it distinguishes a population of lymphocytes that is not defined by any other antigenic system, according to three criteria: (a) representation of Qa-1 cells among T-cell sets defined by Lyt phenotypes, (b) the profile of responses to mitogens exhibited by lymphocyte populations depleted of Qa-1+ cells, and (c) the profile of immune responses of lymphocyte populations depleted of Qa-1+ cells.

Animals↗
PubMed1978

Changes in suppressor mechanisms during postnatal development in mice.

The activity of suppressor cells from spleens of mice of varying ages was assessed by their addition to cultures of normal or SRBC immune spleen cells together with a challenge of SRBC. 1-wk and adult spleen cells were highly suppressive of the secondary in vitro antibody response to SRBC. 3-wk spleen cells were less active in suppressing this response. The nature of the suppression and the character of the suppressor cells changed in this period. Whereas adult spleen cells demonstrated specificity, 1-wk cells nonspecifically suppressed all responses tested. Further, unlike adult suppressor cells (which are Thy.1.2 positive), 1-wk suppressor cells are insensitive to anti-Thy.1.2 treatment in this system. Both cells are nonadherent to glass beads and nylon wool and are undetectable in the normal thymus.

Aging↗
PubMed1977

Two main features of T-cell development: thymus traffic and postthymic maturation.

It appears from the results presented in Table V and discussed in the preceding pages that a precursor population of immunologically competent T cells can be characterized and defined by multiple biological criteria as being probably of postthymic origin and substantially different from either the immunologically competent T lymphocyte or the prethymic stem cells. On the basis of recent data on functional characteristics of of different subsets of T cells, which suggest parallel lines of differentiation (see Chapter 2), it is possibile that the postthymic precursor compartment may also show heterogeneity; however, this cannot be presently asserted from our results.

Aging↗
PubMed1977

Ly phenotype of T cells cytotoxic for syngeneic mouse mammary tumors: evidence for T cell interactions.

Specific cell-mediated cytotoxicity (CMC) of lymph node cells from immunized C3Hf mice, against syngeneic C3H/Umc mammary tumor cells, assayed in vitro, is effected by T lymphocytes. This CMC response is biphasic, with an early peak attained within 6 hr and a second major peak beginning at about 18 hr. Effector cells of both the early minor and late major phases of the response belong to the Ly23 set. Other T cell sets evidently play no part in the early effector response. But specifically activated Ly1 cells help or amplify the major late-phase response. Nevertheless, the mixture of specifically activated Ly1 and Ly23 sets still does not completely reconstitute the late response, which implies that the Ly123 set is also needed for maximal expression of CMC in this system. These Ly123 cells must come from specifically immunized donors. It appears, therefore, that maximal CMC is achieved by the participation of specific Ly123 cells which in the late phase directly or indirectly give rise to Ly23 killer cells. Thus, although killing of syngeneic mammary tumor cells in the CMC assay is invariably effected by cells of the Ly23 set, specifically activated cells of the Ly1 set, and probably of the Ly123 set also, are participants in the interactions needed to produce a maximal CMC response.

Animals↗
PubMed1976

Leukemogenic activity of murine type C viruses after long-term passage in vitro.

Cloned stocks of several murine leukemia viruses (MuLVs) were shown to be leukemogenic for susceptible mice after more than nine years of in vitro passaging in mouse embryo fibroblasts. Tissue culture-grown Rauscher (R-) MuLVs injected into newborn or young adult BALB/c mice induced lymphocytic leukemias in 100% of the animals beginning 80 days post-inoculation. No erythroblastic leukemia was observed even after passaging the tissue-culture-grown R-MuLVs twice through mice, indicating that the component responsible for that disease had been lost or attenuated during growth in fibroblasts. The tissue-culture-grown stock of Moloney (M-) MuLVs likewise induced lymphocytic leukemias in 94% of injected newborn BALB/c mice, and the tissue culture-grown Gross (G-) MuLVs induced lymphocytic leukemias in 42% of injected newborn C3Hf mice. The host range and neutralization characteristics of viruses recovered from animals that became leukemic after injection with the tissue-culture-maintained MuLVs were found to be identical with those of the injected viruses. These data implicate the injected MuLVs in the induction of the leukemias and suggest that the capacity to induce the disease is stably inherited as part of the viral genome even in the absence of expression.

Animals↗
PubMed1976

Cell interactions in the suppression of in vitro antibody responses.

Normal T and immune B lymphocytes interact in a fashion that leads to suppression of the immune response. Normal spleen cells added to cultures of primed spleen cells specifically suppressed both the IgM and IgG secondary antibody response of the primed cells to less than 30% of the response of the immune cells cultured alone. Cell crowding as a possible in vitro artifact was ruled out. The suppression was specific for the priming antigen, even when the specific and nonspecific antigens were included in the same cultures. Suppression required both normal T and immune B cells to be present in culture. We suggest that the immune population produces a signal that can induce normal T cells to become specific suppressor cells. This form of interaction may represent an important regulatory (homeostatic) mechanism in the immune system.

Animals↗
PubMed1976

Growth abnormalities of cultured human skin fibroblasts derived from individuals with hereditary adenomatosis of the colon and rectum.

A heritable propensity to develop malignant lesions is found in individuals with familial adenomatosis of the colon an rectum (ACR) and the Gardner's syndrome variant, an autosomal dominant trait. In the present study, the growth characteristics of cultured skin fibroblasts (SF) derived from normal-appearing flat skin biopsies of ACR families, representing all phenotypes, and appropriate controls were investigated. SF were obtained from stocks between the second and fifth passages and growth to confluency in Eagle's Minimal Essential Medium (EMEM) supplemented with 15% fetal calf serum (FCS). Following trypsinization, cells were replanted in EMEM supplemented with either 1% or 15% FCS at an initial density of 4 x 10(3) cells/cm2 and counted daily for five days. Normal SF representing several age groups (both sexes) and those obtained from non-afflicted individuals of ACR families grew only in 15% FCS. In contrast, SF from ACR subjects and from embryonal skin grew both in 1% and 15% FCS. SF from several clinically asymptomatic adults, children or ACR patients, grew in 1% FCS as well. Cell cultures from ACR individuals showed regions of criss-crossed arrays and multilayered pattern. These growth properties were not observed in normal cell cultures. The SF from ACR individuals did not grow in methocel, nor did they form tumors in athymic mice. These results suggest the occurrence of previously undetected biochemical alterations in SF taken from ACR genotypes.

Animals↗
PubMed1976

Correlation of in vitro and in vivo studies of antigens relevant to the control of murine breast cancer.

The specific immune response of C3H [mammary tumor virus (MTV)] (MTV+) and C3Hf sublines (MTV- or milk-MTV-) to mammary tumors of C3H origin was measured in vitro by the ability of lymphocytes derived from immunized animals to destroy 3H-proline prelabeled target cells after 36 hr of incubation in vitro (lymphocyte:target ratio, 400:1). Primary cytotoxic responses were obtained both in C3H and C3Hf mice and were mediated mainly by T-lymphocytes (Thy.1-positive cells). The degree of cross-reactivity between different C3H mammary tumors showed wide ranges and actually depended on the amounts of MTV-related antigens expressed in the tumor cells. An inverse relationship between MTV-related and H2 histocompatibility antigens was observed. Thy.1.2 antigen (theta-C3H) was also detected on the surface of mammary tumor cells. Both C3H and C3Hf recognized cross-reacting and noncross-reacting antigens in the tumor cells, although the magnitude of the response in the MTV+ mice was lower than in the C3Hf sublines. Soluble antigens could be extracted by 3 M KCl treatment of the tumor cells and could be used as immunogens (eliciting cytotoxic responses against mammary tumor cells), or as stimulators for thymidine uptake (blast transformation in vitro) for specifically immune T-lymphocytes. Attempts to modify spontaneous tumor development in C3H and C3HfA virgin female mice by immunization with formalinized MTV or with soluble antigens extracted from C3H mammary tumors, although still in progress, showed a moderate preventive effect (especially in the C3HfA) immunized with MTV and an acceleration of tumor appearance both in C3H and C3HfA mice immunized with the soluble antigens extracted from C3H mammary tumors. This last set of results, although preliminary, indicates that a better understanding of the immunological events in this system is essential for the design of experiments on prophylaxis of tumor development.

Animals↗