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PubMed1975

Syngeneic adoptive immunotherapy and chemoimmunotherapy of a Friend leukemia: requirement for T cells.

The aim of the study was to determine which cell mediates adoptive immunotherapy and chemoimmunotherapy of a syngeneic transplantable Friend virus-induced leukemia (FBL-3). An adoptive immunotherapy model was developed in which adult C57BL/6 mice given a lethal dose (10(4)) of FBL-3 on day 0 were saved by treatment on day 1 with C57BL/6 spleen cells or peritoneal exudate cells (PEC) immune to FBL-3. Cells passed through a nylon wool column to remove B cells and macrophages or treated with carbonyl iron to remove phagocytic cells remained effective, whereas cells treated with anti-theta serum and complement were far less effective. For adoptive chemoimmunotherapy, mice inoculated with 10(7) FBL-3 were treated 5 days later with cyclophosphamide (CY) plus immune spleen cells. CY, with or without non-immune cells, prolonged survival but all mice died with leukemia, whereas mice given CY plus immune cells survived tumor-free. As an adjunct to CY, immune cells passed through nylon wool or treated with carbonyl iron remained quite effective whereas cells treated with anti-theta serum and complement were far less effective. Thus, immune thymus-derived lymphocytes were required for the adoptive immunotherapy of an early leukemia or chemoimmunotherapy of a disseminated leukemia.

Animals↗
PubMed2001

The adoption of technology in higher/nursing education.

This is a review article on the adoption of technology in higher education. Higher education in general is looked at. Nursing Education is also higher education and therefore it will not be addressed separately, but mentioned in some instances. The article presents a look into how students and lecturers experience change, as well as barriers they perceive in the integration and adoption of technology. Some suggestions are made to the adoption process as well as the necessity for personnel development in information technology. The role that Information Technology personnel play in the adoption and integration process of technology is also discussed.

Computer-Assisted Instruction↗
PubMed2003

Physician attitudes toward strategies to promote the adoption of medical evidence into clinical practice.

BACKGROUND: [corrected] Promoting the adoption of medical evidence into clinical practice has been advocated as one approach to improving healthcare quality and reducing medical errors. Data describing the effectiveness of different strategies to achieve this goal in real-world settings are limited. OBJECTIVE: To determine the effectiveness of selected interventions on the adoption of medical evidence into clinical practice. STUDY DESIGN: A cross-sectional survey of a random sample of physicians selected from the American Medical Association's Physician Master File. PATIENTS AND METHODS: We examined the perceived effectiveness of 7 strategies (represented by 27 individual interventions) and 5 general approaches for promoting the adoption of medical evidence into clinical practice in 1100 practicing physicians. Respondent exposure to interventions was also determined. Regression analyses were performed to identify factors that affected effectiveness ratings. Analysis of variance was used to test the hypothesis of equal mean scores across different comparison groups. RESULTS: Of 1,100 surveys mailed, 63 (5.7%) were excluded and 431 were completed (response rate = 41.6%). Mean +/- SD effectiveness scores for the 27 individual interventions on a 5-point Likert scale ranged from 2.0 +/- 0.9 (literature received from insurance companies and managed care organizations) to 4.2 +/- 0.8 (one-on-one communication with respected colleagues). Ranges for the 7 strategies were 2.6 +/- 1.0 (patient-mediated interventions) to 3.6 +/- 0.9 (educational meetings) and for the 5 general approaches were 1.98 +/- 0.9 (administrative interventions) to 3.3 +/- 0.8 (provider education). The hypothesis of equal mean effectiveness scores was rejected for all comparisons (P < .001). Frequency of exposure was the only variable to predict effectiveness (P < .001 for all regression models). CONCLUSION: From the perspective of practicing physicians, the frequency of exposure to strategies for promoting the adoption of medical evidence into clinical practice strongly affects their perceived effectiveness.

Attitude of Health Personnel↗
PubMed2003

Research to practice: adoption of naltrexone in alcoholism treatment.

Naltrexone, a prescription medication, was approved in December 1994 as an adjunct to counseling in treatment of alcoholism and alcohol abuse, representing the first new medication for alcoholism in several decades. Initial controlled trials indicated that it is effective in preventing relapse, while later trials show mixed results. Although many physicians and others treating alcoholism have found naltrexone to be very helpful in treatment, it is still a technology that has not been used widely. In this study, we examine which clinicians have adopted naltrexone into practice for what reasons, and what clinical and nonclinical factors acted as barriers to its use. In our mail survey of alcoholism treatment clinicians, 80% of physicians and 45% of nonphysicians report prescribing or recommending naltrexone at least rarely, but only 15% of physicians, even among addiction specialists, prescribe naltrexone often. The strongest barriers to adoption of naltrexone were financing and inadequate knowledge about the medication, followed by lack of sufficient evidence regarding effectiveness. Clinicians were most likely to adopt naltrexone if they were affiliated with treatment programs that actively promoted its use. We conclude that in order for a new substance abuse treatment medication to be widely adopted in clinical practice, information about it must be properly directed, clinicians must be convinced of its effectiveness, it must be adequately financed, and the treatment organizations in which clinicians work must promote its use.

Alcoholism↗
PubMed2004

Barriers to EMR adoption in internal medicine and pediatric outpatient practices.

BACKGROUND: Although electronic medical records (EMRs) are widely regarded as valuable tools in patient care, physicians in outpatient practices have been slow to adopt them. We sought to determine the current use of EMRs in area practices and identify physician attitudes related to their adoption. METHODS: Fax and mail survey of randomly selected physician representatives of all outpatient practices of Internal Medicine (n=51) and Pediatrics (n=24) in Shelby County, Tenn. Scores on eight physician attitudes regarding barriers to EMR adoption were obtained using a Likert scale. RESULTS: Survey response rate was 55%, with 18% reporting current EMR use. This corresponds to an EMR penetration of 20% for Shelby County. Current users were significantly less likely (P=0.005) than non-users to feel that an EMR interferes with doctor-patient interaction and less likely (P=0.019) to have EMR privacy concerns. While differences noted in other attitudes did not reach statistical significance, a trend was seen toward EMR users being less concerned (P=.0502) about reliability of an EMR. Large practices were no more likely than smaller ones to be using an EMR. Internal Medicine and Pediatric participants responded similarly to all items. The number of years in practice had no demonstrable impact on physician responses to these survey items. CONCLUSIONS: In this West Tennessee physician population, EMR user and non-user attitudes markedly differed about impact on doctor-patient interaction and patient privacy. If such concerns could be addressed to the satisfaction of physicians considering EMRs in their practice, adoption rates might be increased.

Ambulatory Care Information Systems↗
PubMed1990

The life cycle of an innovation: adoption versus discontinuation of the fluoride mouth rinse program in schools.

Reasons for adoption and for discontinuation of a dental caries prevention innovation (the fluoride mouth rinse program) are examined by using recent theory on decision processes within organizations. Greer's (1977) analysis of three theoretical approaches for the study of innovation adoption--classical, organizational, and political--are used as an organizing framework to analyze these two parts of an overall life cycle for innovations. The results from both descriptive and multivariate analyses support the relevance of "political" and "classical" diffusion models for both adoption and discontinuation. Organizational structure variables--e.g., demographic indicators, administrative structures, and financial measures--show little explanatory strength for either outcome. Both outcomes seem to be dominated by "political" influences from strong interpersonal communications rather than by formal decision-making processes. The results suggest that political contingency theories may explain the processes by which organizations adopt and discontinue innovations, whereas classical diffusion theory explains the content of these processes.

Dental Caries↗
PubMed1990

Radiosensitive barrier to T-cell-mediated adoptive immunotherapy of established tumors.

This study shows that it is not possible to cause regression of the immunogenic SA-1 sarcoma by adoptive immunotherapy with tumor-sensitized T-cells, unless the tumor-bearing recipient is exposed to a sublethal dose of gamma-irradiation to remove a barrier that prevents adoptive immunity from being expressed. This barrier to adoptive immunotherapy was found to be regenerated between 2 and 4 weeks following irradiation, and its regeneration was associated with general repopulation of host T-cells. However, it was not regenerated in the absence of the thymus, thus showing that it is T-cell dependent. Evidence that it is caused by the presence of CD4+ suppressor T-cells was shown by the finding that it can be removed by depleting mice of CD4+ T-cells with anti-L3T4 monoclonal antibodies, but not by depleting them of CD8+ T-cells with anti-Lyt-2 monoclonal antibodies. Again, the barrier could be restored to irradiated recipients by infusing them with CD4+ T-cells, but not with CD8+ T-cells, from tumor-bearing donors. The barrier to adoptive immunotherapy was found to be tumor induced and to be paradoxically generated in concert with host concomitant immunity.

Animals↗
PubMed1989

[Adoptive immunotherapy in patients with medulloblastoma by LAK cells].

Medulloblastoma is one of the most popular malignant brain tumors in children. It accounts for about 15% of all pediatric brain tumors. Radiochemotherapy has prolonged the 5-year survival rate up to 60-85% for patients with medulloblastoma. But the conventional therapy is not so effective to recurrent cases, especially with meningeal dissemination, and generally fatal. There remains a big problem of the neurotoxicity to infants in a growth process under the whole-neuraxis irradiation and chemotherapy. Aiming to relieve the radiation and antitumor drugs, adoptive immunotherapy is greatly expectant. We have had clinical trials of adoptive immunotherapy for 8 patients with medulloblastoma by lymphokine-activated killer (LAK) cells. They were from 2-9 years in age and had cerebrospinal fluid (CSF) dissemination of the tumors. All patients underwent the whole-neuraxis irradiation and chemotherapy. After they had CSF dissemination, they were submitted to an adoptive transfer of allogeneic LAK cells. LAK cells were induced from peripheral blood lymphocytes (PBL) of their relatives with human recombinant interleukin-2. 3-15 x 10(9) LAK cells were transferred intrathecally in 2-3 months. In 3 of 8 patients, neurological signs were improved and malignant cells had never been detected on CSF cytology after the adoptive immunotherapy. One among these 3 patients showed complete response in 20 months. Thus, this is an attractive treatment for patients with medulloblastoma, especially with CSF dissemination, which cannot be cured by current therapeutic intervention.

Brain Neoplasms↗
PubMed1989

[Successful adoptive immunotherapy with OK432-inducible activated natural killer cells on tumor-bearing mice].

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo prime and subsequent in vitro challenge with the streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy 1+, asialo GM1+, suggesting the activated NK cells (OK-NK cell). The culture supernatants of spleen cells with OK432 possessed the activity of IL-2 and IFN-gamma, and the IL-2 played a major role to induce the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on tumor-bearing mice. The mice were implanted SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously (s.c.) to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or i.t., adoptively. By the adoptive transfer of OK-NK cells, the 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was increased, significantly. The intratumoral remnants of 125I-labelled OK-NK cells were 61.27 and 8% after intratumoral transfer, respectively. By multiple transfer of OK-NK cells the anti-tumor effect was more augmented than that of a single transfer. Thus we recognized the anti-tumor effect of adoptive transfer of OK-NK cells on tumor-bearing mice, and suggested that OK-NK cells could be useful for the therapy of cancer patients.

Adenocarcinoma↗
PubMed1988

Adoptive cell transfer studies to examine the role of T lymphocytes in immunity to Trypanosoma musculi.

Previous studies in this laboratory utilizing monoclonal antibody-induced immunosuppression have demonstrated that the T-helper lymphocyte is primarily responsible for the T lymphocyte dependency of Trypanosoma musculi elimination from the bloodstream of mice, and that T-cytotoxic lymphocytes play a minimal role in this response. In the current study, these findings were extended by examining the effects of adoptive cell transfers on the course of infection with T. musculi using immune splenocytes enriched for T lymphocyte subpopulations. These studies demonstrated that adoptive transfer of immune splenic T lymphocytes resulted in a specific, dose-related enhancement of kinetics of trypanosome elimination. This effect was found to be due to the presence of L3T4+ T-helper cells in the immune splenocyte population. Adoptive transfer of Lyt-2+ T-cytotoxic cells or lymphokine-activated killer (LAK) cells was ineffective in altering the course of infection. In addition, it was found that immune B lymphocytes were equally capable of adoptively transferring immunity to T. musculi, suggesting that the primary role of the T-helper lymphocyte is to provide help in the induction of parasite-specific antibodies.

Animals↗
PubMed1977

Pathogenesis of experimental allergic orchitis. III. T lymphocyte requirement in local adoptive transfer by peritoneal exudate cells.

In experimental allergic orchitis (EAO), a lesion characterized by mononuclear invasion of seminiferous tubules can be adoptively transferred within 1 to 4 days by testicular injection of peritoneal exudate cells (PEC) from syngeneic strain 13 guinea pigs (GP) immunized with homologous testicular antigens in complete Freund's adjuvant (CFA). This study examined the role of T lymphocytes, macrophages, and polymorphonuclear neutrophils (PMN) in the adoptive transfer. Guinea pig PEC contained 7% T lymphocytes, rare B lymphocytes, and over 90% of macrophages and PMN. After T lymphocytes were depleted by rabbit erythrocyte (E) rosette and Hypaque-Ficoll gradient centrifugation, cell preparations that contained 73% of original macrophages and 15% original T lymphocytes were obtained, and these cells did not transfer EAO (0 of 18 testes). In contrast, cell preparations enriched in T lymphocytes by nylon wool column or E rosette contained 1.5% of the original macrophages and 59% of the original T lymphocytes transferred EAO to 70% of the testes, starting at 1.5 x 10(6) T lymphocytes per testis. The number of T lymphocytes correlated with the incidence of adoptive transfer; the correlation existed regardless of the number of macrophages or PMN present. Finally, EAO was adoptively transferred to recipients that had total-body irradiation. The results indicate that (a) T lymphocytes are capable of transferring lesions of EAO, (b) in the transfer, the T lymphocytes did not function as helper T cells, since the transfer need not involve participation of host lymphoid cells, and (c) by inference, testis antigen-reactive T lymphocytes exist.

Animals↗
PubMed1986

Expression of MEL-14 antigen is not an absolute requirement for dissemination to lymph nodes after adoptive transfer of murine T lymphocyte clones.

The inability of established antigen-specific murine T lymphocyte clones to recirculate well in vivo has been attributed to loss of the surface glycoprotein gp90MEL-14, which is important for specific adherence to post-capillary high endothelial venules in peripheral lymph nodes (LN). Defective recirculation of clones may contribute to inefficient adoptive immunotherapy when compared with fresh immune spleen or LN populations. To optimize models of adoptive immunotherapy, we sought to improve recirculation of Thy-1.2+, L3T4+ clones by inducing reexpression of MEL-14 antigen (gp90MEL-14). Clones were analyzed after treatment with differentiating agents, incubation in the presence or absence of recombinant interleukin 2 (rIL 2), coincubation in vitro with nonirradiated Thy-1.1 LN or thymus cells, or adoptive transfer into Thy-1.1 hosts. We were unable to demonstrate induction of gp90MEL-14 in any case. However, although clones remained MEL-14 negative, they were able to disseminate widely after subcutaneous adoptive transfer in the presence of clone-specific antigen and rIL 2 into Thy-1.1 mice pretreated with cyclophosphamide. Withdrawal of exogenous rIL 2 was associated with rapid disappearance of clones from all sites. We conclude that murine T cell clones undergo a step in terminal differentiation that precludes surface expression of gp90MEL-14 and that these clones would be unlikely to provide a source of long-lived recirculating memory T lymphocytes. However, under appropriate circumstances it is possible for antigen-specific clones to disseminate widely among host LN and mediate short-term immune responses.

Animals↗
PubMed1985

Eradication of a disseminated syngeneic mouse lymphoma by systemic adoptive transfer of immune lymphocytes and its dependence upon a host component(s).

We have studied the in vivo effects of carrageenan and trypan blue on the adoptive immunotherapy of an established local and disseminated syngeneic mouse FBL-3 lymphoma. Mice receiving 500 rads total-body irradiation before injection of FBL-3 tumor into the footpad were treated 4 to 5 days later when a palpable local tumor and disseminated metastases were present. Injection of in vivo immune lymphocytes i.v. caused complete regression of footpad tumor and cured 96% of all mice (greater than 60 days mean survival; p less than 0.0005). Carrageenan or trypan blue treatment of the tumor-bearing host abrogated the therapeutic effect of adoptively transferred cells. Cure rates were significantly reduced to 27% (p less than 0.004) and 0% (p less than 0.0001) and mean survival times to 40.2 days (p less than 0.0005) and 15.2 (p less than 0.005) days for mice treated with carrageenan and trypan blue, respectively, in addition to immune cells. In vivo treatment of the immune spleen cell donors with carrageenan or trypan blue had no significant effect on the ability of those splenocytes to mediate cure when adoptively transferred into tumor-bearing hosts, indicating that the inhibitory activity of these agents cannot be attributed to direct toxicity to immune lymphoid cells. These results demonstrate that a recipient component(s), possibly macrophages, sensitive to carrageenan and to trypan blue but relatively resistant to radiation (500 rads), plays a vital role in the cure of tumor-bearing mice that receive the adoptive transfer of immune splenocytes.

Animals↗
PubMed1984

Analysis of the involvement of cells from donor and recipient mice in adoptive transfer of antitumor immunity.

In this study, we attempted to analyze the effector cells for adoptive transfer of protective immunity directed against a P815Ys tumor. The spleen, lymph node, and peritoneal exudate cells obtained from immune mice at Day 7 to Day 10 after last challenge were tested for their in vitro cell-mediated cytotoxicity against P815Ys cells, using a 4-hr 51Cr release assay. The immune spleen lymphocytes (ISL) showed no cytotoxicity, whereas the peritoneal exudate cells exhibited marked cytotoxicity. Unexpectedly, when ISL or peritoneal exudate cells were adoptively transferred i.v. into mice bearing the P815Ys tumor, it was the ISL but not the peritoneal exudate cells that provided the hosts with significant protection. Using alloantibodies for negative depletion of cells in ISL, it was found that, after treatments with anti-Thy 1.2 or anti-Lyt 1 antiserum plus complement but not with anti-Lyt 2 or complement alone, the protective capacity of ISL can be abolished, indicating that the effector cells for conferring protective immunity to the host are Lyt 1-bearing T-cells. Moreover, culture supernatants of ISL with or without mitomycin C-treated P815Ys contain helper factor, interferon, and interleukin 2, which enhanced the in vitro generation of cell-mediated cytotoxicity against P815Ys. Taken together, these results strongly suggest that the donor helper T-cells are the effector cells responsible for adoptive transfer of protective immunity. We next examined the contribution of host cells. Syngeneic mice were made to become either T-cell (with thymectomy and irradiation)- or macrophage (with the administration of silica) depleted and were then subjected to adoptive transfer experiments. Both the thymectomized and the silica-treated mice, after receiving the ISL, showed significantly better survival times than did normal mice. Thus, the data suggest that the elimination of T-cells or inactivation of macrophages, presumably with immunosuppressive activity in the recipients, will allow further improvement of their battle for survival against tumor.

Animals↗
PubMed1978

A protocol for the adoption of analytical methods in the clinical chemistry laboratory.

The demand on the clinical chemistry service laboratory to continually adopt more precise and accurate methodologies makes it mandatory for the service laboratory to have a systematic protocol for evaluating and adopting new assay methods. A protocol is presented for adopting clinical chemistry methods in the service laboratory, with emphasis on spectrophotometric determinations. The recommended protocol may be used to evaluate alternate procedures to those currently in use as well as procedures for additional analytes. We present those critical points to be considered in method adoption and instruction for the resolution of each point.

Chemistry Techniques, Analytical↗
PubMed1984

Effector mechanisms operative in adoptive therapy of tumor-bearing animals: implications for the use of interleukin-2.

Disseminated tumors growing progressively in syngeneic hosts can be eradicated by combination therapy with cyclophosphamide and adoptive transfer of specifically immune T cells. Interleukin-2 (IL-2), which induces proliferation of T cells specifically activated by antigen, has substantial therapeutic potential as a reagent for increasing the magnitude of tumor-specific T cell responses. The purpose of the present studies was to determine the effector mechanisms operative in tumor-bearing hosts by which subpopulations of immune T cells can mediate tumor eradication, and to determine if the in vivo administration of exogenous IL-2 can augment these T cell effector functions. Disseminated leukemia was eradicated by adoptive therapy with the immune Lyt 1+2- noncytolytic T cell subpopulation, under experimental conditions in which cytolytic T lymphocytes could not participate. The Lyt 1+2- subset contains helper/amplifier cells that produce endogenous IL-2 in response to tumor and effector cells that mediate delayed-type hypersensitivity reactions. The administration of exogenous IL-2 following transfer of immune T cells containing this noncytolytic subset failed to augment their therapeutic activity, implying that the amount of IL-2 being produced endogenously did not limit the antitumor response. Adoptive therapy with purified cytolytic Lyt 1-2+ T cells produced a demonstrable but limited antitumor effect. Since this cytolytic subpopulation lacked helper T cells, the limited activity observed presumably reflected a requirement for an IL-2-producing cell. Administration of exogenous IL-2 following cell transfer satisfied this requirement and markedly augmented the efficacy of adoptive therapy with Lyt 1-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Adoptive immunotherapy of cancer: accomplishments and prospects.

Adoptive immunotherapy is an approach to cancer treatment that has not received significant evaluation in cancer patients. Recent developments in modern cellular immunology have expanded the opportunities for utilizing adoptive immunotherapy in humans. A variety of animal models have been developed utilizing the adoptive transfer of immune cells that can mediate the regression of established murine tumors. Analyses of these models are defining the important criteria necessary for the application of this approach to humans. Studies of the immune response of human cells to autologous tumors are identifying cells with antitumor reactivity that may be of value in the treatment of human malignancy. Preliminary clinical studies have been performed demonstrating the feasibility of infusing large numbers of activated lymphoid cells into humans. Adoptive immunotherapy is an approach to the treatment of cancer that deserves further study.

Animals↗
PubMed1981

Adoptive immunity to the guinea pig line 10 hepatoma and the nature of in vitro lymphoid-tumor cell interactions.

Adoptive transfer of spleen cells from specifically immunized donors to nonimmunized recipients was used to study tumor immunity in vivo to the syngeneic line 10 guinea pig hepatoma. Hepatoma cells cultured as monolayers on fibronectin-coated surfaces served as targets for immune splenocytes in a 3H release cytotoxicity assay in vitro. An antigenically distinct syngeneic guinea pig hepatoma (line 1) was used to study the specificity of adoptive systemic immunity and of the cytotoxicity in vitro. The protection afforded by adoptive immunization against challenge with hepatoma cells was tumor line specific, while in most cases cytotoxicity in vitro was not. The in vitro cytotoxic effect was abolished after absorption of the immune spleen cells with monolayers of either line 10 or line 1. In contrast, the in vivo tumor-specific rejection activity of line 10 immune spleen cells was depleted after absorption with line 10 but not with line 1 or other control monolayers. These studies revealed that the immune cells mediating cytotoxicity in vitro were functionally distinct from those conveying adoptive protection in vivo. Immune cells possessed receptors for tumor-specific rejection antigens on hepatoma cells, and their interaction did not lead to destruction of the neoplastic cells in vitro.

Animals↗