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PubMed1982

The effect of cyclosporin A on the adoptive transfer of experimental allergic encephalomyelitis in the Lewis rat.

Experimental allergic encephalomyelitis (EAE) can be adoptively transferred in Lewis rats with spleen cells from immunized animals, after culture with concanavalin A or myelin basic protein (MBP). The effect of the immunosuppressive drug cyclosporin A (CsA) on the in vitro and in vivo steps of the cell transfer has been investigated. Clinical signs of EAE were completely suppressed by CsA in rats immunized with MBP in Freund's complete adjuvant and spleen cells from these animals, cultured with the antigen, did not transfer the disease. The incidence of transferred disease was also reduced, if recipients were treated with CsA, although a higher dose of drug than that needed to suppress active EAE was required. In both instances complete suppression of EAE was only accomplished for the period of dosing, although the clinical signs of disease which appeared after withdrawal of the drug were significantly reduced in severity. These results imply that an immune response in the host animal is a prerequisite for adoptive transfer of EAE or suggest that CsA can regulate the action of lymphocytes already primed.

Animals↗
PubMed1983

Autoimmune effector cells. V.A monoclonal antibody specific for rat helper T lymphocytes inhibits adoptive transfer of autoimmune encephalomyelitis.

The in vitro activation of spleen cells from donor rats immunized with myelin basic protein results in enhanced adoptive transfer of experimental allergic encephalomyelitis to syngeneic recipients. In this study, adoptive transfer was inhibited when monoclonal antibody W3/25, which defines an antigen on rat helper T lymphocytes, was included in the in vitro cultures. Partial inhibition was achieved with monoclonal antibody OX-3, which recognizes la antigen, whereas other anti-T cell monoclonal reagents were ineffective. These results support the conclusion that W3/25+T cells play an essential role in the induction of this autoimmune response.

Animals↗
PubMed1984

Adoptive transfer of delayed type hypersensitivity reactions specific for Leishmania major antigens to normal mice using murine T cell populations and clones generated in vitro.

Leishmania major specific murine T cell blasts and clones maintained in vitro were tested for their ability to adoptively transfer delayed type hypersensitivity (DTH) reactions to normal mice. These effector cells exhibited a Lyt 1+2- cell surface phenotype. They induced specific DTH reactions in syngeneic DBA/2 mice after local transfer in the footpad, (together with parasite antigens) or intravenous injection followed by challenge with parasite antigens in the footpad. The DTH reactions were specific for L. major antigens and required H-2 identity between the injected T cells (clones) and the adoptively transferred host. Using radioactively labelled T cell blasts for intravenous transfer, it was demonstrated that a large fraction of these functionally active cells localized in the spleen and footpad which had been challenged with parasite antigens.

Animals↗
PubMed1984

A possible explanation for the synergism between mixed T- and B- cell populations in mice adoptively immunized with Ancylostoma caninum.

Ancylostoma caninum--mouse model was employed to study the cellular cooperation in the adoptive immune response. The syngeneic recipient mice were intraperitoneally injected once or twice with mixtures of thymus and bone marrow cells from infected (with 500 or 2000 larvae) and uninfected donors. The experimental recipients expelled and/or destroyed the challenge larval burden more readily and at a greater rate than the controls with unsensitized cells. The cooperation between sensitized thymus and bone marrow cells was, thus, found to be exposed in a better manifestation of adoptive immune response than either of these two alone. The cellular elements of delayed hypersensitivity after combining with the antibodies of humoral system could elicit a much better response in these recipients.

Ancylostoma↗
PubMed1981

Adoptive transfer of immunity to Histoplasma capsulatum in athymic nude mice.

Studies of adoptive transfer of resistance to Histoplasma capsulatum were performed with athymic nude (nu/nu) recipients and heterozygous (nu/+) donor mice. This model has the benefit of employing a recipient mouse (nu/nu) which cannot be immunized actively against H. capsulatum. Nu/nu mice were protected against H. capsulatum by whole spleen cells, fractioned T lymphocytes, and macrophages from immunized nu/+ donor mice. Similar cell populations from nonimmune nu/+ mice were not protective. Treatment with gold sodium thiomalate, an inhibitor of macrophage function, increased susceptibility to H. capsulatum in nu/+ and nu/nu mice. Adoptive transfer of immunity to H. capsulatum is multifactorial and depends on both T lymphocytes and macrophages.

Animals↗
PubMed1984

Specific adoptive immunotherapy with tumor-specific cytotoxic T-lymphocyte clone for murine malignant gliomas.

The efficacy of glioma-specific cytotoxic T-lymphocyte for a syngeneic murine malignant glioma (a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma) was investigated. The cytotoxic clone (G-CTLL 1), established and expanded exponentially by T-cell growth factor, has retained target specificity for more than 6 months. In adoptive therapy and Winn assay, the in vivo antitumor activity of G-CTLL 1 was demonstrated against mice inoculated intracranially with 203-glioma cells. The therapeutic effects in adoptive immunotherapy were largely dependent on dose and time of i.v. administration, although the therapy was rather ineffective in condition of increased intracranial pressure due to the tumor growth. The mechanisms responsible for the in vivo protection were probably related to the killing activity of G-CTLL 1 or the tumor-specific production of immune interferon by G-CTLL 1.

Animals↗
PubMed1984

Cardiac nuclear imaging. Adoption of an evolving technology.

A national survey was conducted to examine the extent of adoption and use of nuclear imaging procedures in cardiology in hospitals by 1979 and to develop estimates for 1983. The data are based on the responses of 171 hospitals from a representative 200-hospital sample stratified for region, bed-size, and teaching status. Extrapolating the data, it is estimated that 2,106 hospitals nationally use cardiac nuclear imaging. In 1979, hospitals with at least 200 beds performed an estimated 396,000 cardiac nuclear imaging studies at a cost of $93 million. By 1983, it is estimated that 4,061 hospitals had the capability to perform cardiac nuclear imaging and that national expenditures would exceed $200 million ( noninflated dollars). Although cardiac nuclear imaging procedures have been demonstrated to be valuable in detecting coronary artery disease or measuring ventricular function, these procedures were rapidly being adopted by the medical community at a time when only limited information about their effectiveness and efficiency are available.

Cardiology↗
PubMed1982

Mechanisms of immunologic eradication of a syngeneic guinea pig tumor. I. Quantitative analysis of adoptive immunity.

Adoptive immunity against a syngeneic hepatoma (line-10) of Sewall-Wright inbred strain 2 guinea pigs was analyzed by a two-dimensional titration of iv transferred immune lymphoid cells versus intradermal tumor challenges. Tumor resistance increased exponentially as a function of the number of immune lymphoid cells transferred. Within the tumor challenge doses analyzed, suppression of tumor growth mediated by the transferred immune lymphoid cells appeared to be independent of the primary immune response in the recipient. Quantitatively, rejection of a given number of tumor cells reflected the number of transferred immune cells and was independent of the presence of the same tumor at other skin sites. There was no evidence indicating that transferred immune cells were attracted specifically to the tumor inoculation site. The number of tumor cells that could be rejected at a skin site by adoptive immunity was greater than the estimated number of immune lymphoid cells present at the challenge site.

Animals↗
PubMed1980

[Effect of anti-brain sera on the appearance of hypersensitivity of the delayed type and its adoptive transfer].

The effect of rabbit immunosera against CBA mouse brain on lymphoid cells of guinea pigs was studied in experiments with adoptive transfer of hypersensitivity of the delayed type. In vitro treatment of the transferred cells abolished their capacity for adoptive transfer. Such an effect of the sera was not selective with respect to the sensitizing antigen, i. e. it was nonspecific. Pretreatment with sera blocked the development of local allergic reactions of the delayed type and did not affect reactions of the immediate type.

Animals↗
PubMed1982

Development of long-term cell lines and lymphoid clones reactive against murine and human tumors: a new approach to the adoptive immunotherapy of cancer.

We have investigated the use of T-cell growth factor (TCGF) to isolate and grow, in long-term culture, lymphoid cells with immunologic reactivity directed against syngeneic murine and autologous human tumors. Splenocytes from mice immune to a methylcholanthrene-induced sarcoma were expanded in TCGF, both before and after in vitro mixed lymphocyte-tumor cultures, and expressed high levels of cytotoxicity for fresh syngeneic solid tumor cells. Cloned lines have been isolated with a high level of specific lysis for the immunizing tumor. Similar studies of cytotoxic reactivity to a syngeneic FBL-3 lymphoma have given rise to long-term cytotoxic cell lines growing in TCGF capable of curing mice with disseminated lymphoma in adoptive transfer studies. Exposure to TCGF, of human peripheral lymphoid cells from cancer-bearing patients, results in the development of cytotoxicity to autologous fresh tumor. We have used clonal analysis by limiting dilution techniques to isolate individual cloned cells with this autologous antitumor reactivity. Infusion to autologous cytotoxic cells expanded 10,000-fold in TCGF and labeled with 111In into three cancer patients resulted in cell localization initially to the lung and subsequently to the liver and spleen. The application of these techniques for the cloning and expansion of antitumor T-lymphoid cells in TCGF has offered a new approach to adoptive immunotherapy.

Animals↗
PubMed1982

Intracerebral adoptive immunotherapy of a murine lymphoma antigenically altered by drug treatment in vivo.

Intracerebral tumor neutralization assay and adoptive immunotherapy with in vivo sensitized lymphocytes were done in immunodepressed mice challenged intracerebrally with L5178Y/DTIC lymphoma, a tumor subline antigenically altered by treatment with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) in vivo. Primary cytotoxic T-lymphocytes (CTL) were generated in vitro against L5178Y/DTIC cells with the use of splenocytes of histocompatible (BALB/cCr X DBA/2Cr)F1 donors. The extent of antitumor activity of CTL was evaluated by the measurement of tumor cell proliferation in the brain, as judged by the 125I-labeled 2'-deoxyuridine uptake values and by survival times of recipient mice. The results of the experiments showed: a) CTL were highly effective in inhibiting tumor growth when they were injected along with L5178Y/DTIC tumor cells in a Winn-type neutralization assay; b) the tumor inhibition mediated by CTL was specific, since no antilymphoma effects were detected when CTL sensitized against L5178Y/DTIC line were admixed with the parental L5178Y tumor or with other unrelated lymphoma cells; and c) local adoptive immunotherapy with CTL given on day 1, 3, or 5 after the intracerebral challenge with L5178Y/DTIC lymphoma substantially impaired tumor cell proliferation and significantly increased survival times of recipient leukemic mice.

Animals↗
PubMed1982

Adoptive transfers of transplantation tolerance in genetically different strain combinations of mice.

Neonatal transplantation tolerance was induced in strain combinations of mice involving differences in the H-2D or H-2K regions, in the K or D ends of H-2, or in the central I region of the H-2 complex. Attempts were made to transfer the tolerance adoptively by suppressor cells to syngeneic non-immunosuppressed recipients. Adoptive transfer of tolerance was successful only in the combination with H-2D region disparity, and significant but short-lasting prolongation of skin allograft survival time was also obtained in the combination disparate at the D end of H-2. Transfers of tolerance were not successful in the combinations involving differences in the K or I regions of the H-2 complex irrespective of whether cells were transferred one day before or four days after skin grafting. The results are discussed with respect to hitherto known antigenic and tolerogenic properties of individual H-2 regions.

Animals↗
PubMedDate not supplied

Enhancing the effectiveness of media messages promoting regular breast self-examination: messages based on innovation adoption principles.

As public health departments have come to rely more and more on the mass media for the promotion of healthful behavior, it has become increasingly desirable to determine the motivating capability of the messages used in this promotion. A fact that is well understood is that many times any message at all is better than none. However, the effectiveness of various media health messages has not been well researched.A study was therefore undertaken of the comparative effectiveness of two different messages describing how to do a breast self-examination. An "experimental message" for the study was designed by applying the principles that facilitate innovation adoption to the message's format and presentation. This message's impact was then compared with that of the American Cancer Society's pamphlet "How To Examine Your Breasts." This pamphlet had been mailed to a sample of women similar to those receiving the experimental message, but who lived in a different geographic area. The use in each area of control groups who had received no messages afforded an opportunity to study maturation effects (other factors than the mailings that might have influenced study results).The experimental message proved more successful in persuading women to adopt breast self-examination than the comparison message. The women who reported a change in breast self-examination practice following the mailing could be characterized as having a more extensive social support system to promote breast examinations and as having a pre-experiment perception that breast self-examination was a complex practice to perform repeatedly at regular intervals.

Breast Neoplasms↗
PubMed1995

Gamma delta T cells in normal spleen assist immunized alpha beta T cells in the adoptive cell transfer of contact sensitivity. Effect of Bordetella pertussis, cyclophosphamide, and antibodies to determinants on suppressor cells.

Our prior studies showed that gamma delta T cells were required to assist alpha beta T cells in the successful adoptive cell transfer of contact sensitivity (CS) responsiveness. These TCR-gamma delta+ regulatory T cells in immune spleen and lymph node were CD3+, CD4-, CD8+, nonantigen-specific, and non-MHC-restricted. In the current work, experiments were conducted to determine the mechanisms of how the gamma delta T cells were required to assist the alpha beta T cells in CS. We found that similar regulatory gamma delta T cells were in the spleen of normal mice, but not in the spleen of nude nor SCID mice, suggesting that the regulatory gamma delta T cells were present before immunization and required the thymus for differentiation, and also required rearrangements of gamma delta V gene segments. Treatment of cell transfer recipient mice with Bordetella pertussis (Bp), or with a low dose of cyclophosphamide (50 mg/kg), restored the ability of alpha beta+ gamma delta- T cells to transfer CS. This and other results suggested that Bp caused the CS-assisting gamma delta T cells to leave the lymphoid organs (such as the spleen) and enter the circulation, and only then to be able to assist the TCR-alpha beta+ CS-effector T cells. This effect needed the simultaneous i.v. injection of the CS-effector alpha beta T cells and the CS-assisting gamma delta T cells. The results also suggested that treatment with cyclophosphamide inactivated suppressor T cells in the recipients that acted to inhibit the alpha beta T cell transfer of CS, and thus that the CS-assisting gamma delta T cells acted by protecting the CS-effector alpha beta T cells from this endogenous suppression. This suppression of CS transfers also was eliminated by treatment of recipients with two different mAbs to determinants on suppressor T cells. In conclusion, we have described regulatory TCR-gamma delta+ CS-assisting/protecting T cells that are non-antigen-specific, non-MHC-restricted, CD3+, CD8+ gamma delta T cells that may assist adoptive transferring CS-effector alpha beta T cells by making these effector T cells resistant to suppressor T cells in the normal recipients.

Animals↗
PubMed1994

Structural and functional analysis of the NF-kappa B p65 C terminus. An acidic and modular transactivation domain with the potential to adopt an alpha-helical conformation.

The p65 subunit of the NF-kappa B transcription factor contains in its C-terminal 120 amino acids at least two transcription activation domains. One domain (TA1) is contained within only the 30 C-terminal amino acids. Structural studies employing CD and NMR spectroscopy revealed that the TA1 domain is unstructured. NMR analysis of a protein corresponding to the C-terminal 123 amino acids also showed a random coil conformation. However, a portion of TA1 was found to adopt an alpha-helical conformation in the presence of hydrophobic solvents. Transcriptional analysis of point mutants revealed the functional importance of two evolutionary conserved sequence repeats, which are located in the conditionally alpha-helical region of TA1. These repeats acted synergistically in transcription activation. The inhibitory effect of some mutants indicated secondary structure constraints on TA1 in intact cells. Inverting the sequence of two acidic activation domains significantly reduced their transactivating potential, suggesting that amino acid composition is not solely essential for activity; a defined primary structure is necessary as well. Acidic sequence motifs related in primary structure and squelching activity to those of TA1 are present in the activation domains of VP16, c-Rel, and several other transcription factors. We propose a model suggesting that primarily unstructured acidic activation domains can adopt a secondary structure upon contacting their target molecules by an "induced fit" mechanism.

Amino Acid Sequence↗
PubMed1994

Adoption of information technology enabled innovations by primary care physicians: model and questionnaire development.

A survey instrument was developed based on a model of the substantive factors influencing the adoption of Information Technology (IT) enabled innovations by physicians. The survey was given to all faculty and residents in a Primary Care teaching institution. Computerized literature searching was the IT innovation studied. The results support the role of the perceived ease of use and the perceived usefulness of an innovation as well as the intent to use an innovation as factors important for implementation. The model and survey instruments developed show significant potential to enhance our understanding of the process of implementing IT innovations such that Physicians will adopt them.

Attitude to Computers↗
PubMed1995

Host CD4+ T lymphocytes are required for the synergistic action of interferon-alpha/beta and adoptively transferred immune cells in the inhibition of visceral ESb metastases.

Effective adoptive immunotherapy of immunocompetent DBA/2 mice challenged i.v. with the highly metastatic ESb T-cell lymphoma required the combined treatment of recipient mice with tumor-sensitized spleen cells and IFN-alpha/beta. In contrast, immune spleen cells and IFN-alpha/beta treatment did not increase the survival time of ESb-injected DBA/2-nu/nu mice, DBA/2-bg/bg mice, or normal DBA/2 mice injected with antibody to CD4. Treatment of immunocompetent DBA/2 mice with antibody to asialo-GM1, silica, dichloromethylene diphosphonate-containing liposomes, or 500 rads whole-body gamma-irradiation did not diminish the antimetastatic action of ESb-immune cells and IFN-alpha/beta. These results indicate that adoptively transferred immune T lymphocytes and IFN-alpha/beta act together with host CD4+ T lymphocytes/factors to inhibit ESb visceral metastases. Combined treatment with ESb-immune cells together with interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor did not increase the survival time of normal DBA/2 mice challenged with ESb cells. In contrast, IL-12, which had only a slight antimetastatic effect when administered alone, did synergize with ESb-immune spleen cells and increased the survival time of ESb-challenged mice to a similar extent as did IFN-alpha/beta and immune spleen cells. Treatment of DBA/2 mice with potent antibody to IFN-alpha/beta did not abrogate the capacity of IL-12 and ESb-immune spleen cells to inhibit ESb metastases. Unlike immunotherapy with ESb-immune cells and IFN-alpha/beta, ESb-immune cells together with IL-12 inhibited ESb metastases in immunodeficient DBA/2-bg/bg mice.

Animals↗
PubMedDate not supplied

Innovation adoption: introducing I.V. patient controlled analgesia to the nursing workplace.

Technology in the nursing workplace is inevitable but what is not certain is how well these technologies will be initially accepted by nurses. One technological innovation that has appeared in some Canadian hospitals is IV Patient Controlled Analgesia (IV PCA), an innovative technique for pain management, employing the use of a computer-driven pump. Few nursing studies have examined the adoption of technological innovations. This qualitative study examines the incorporation of IV PCA to the nursing workplace and job-related factors that influenced it. A five-phase integration process was identified along with factors impacting on this process. Incorporating IV PCA into nursing practice involved the nurses' judgements of the influence of this innovation on the nurses' comfort with care delivery; the patient/nurse relationship; managing the technology; and the relationship with other health care professionals and patients' family/visitors. Anxiety accompanied the integration process, peaking as IV PCA was introduced to patient care. Findings of this study suggest that actions and decisions initiated by nurse administrators and educators have the potential to influence the successful adoption of this innovation.

Adult↗