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PubMed1984

Use of adoptive transfer and Winn assay procedures in the further analysis of antiviral acquired immunity in mice protected against Friend leukemia virus-induced disease by passive serum therapy.

Previous studies have demonstrated that spleen cells from DBA/2 mice protected against challenge with a leukemogenic dose of Friend leukemia virus (FLV) by passive administration of xenogeneic antiviral or anti-FLV Mr 71,000 viral envelope glycoprotein antisera can adoptively transfer antiviral resistance to unimmunized irradiated syngeneic recipients. In addition, elimination of T-cells by treatment with anti-Thy 1.2 antibodies plus complement had no effect on the ability of spleen cells from serum-protected mice to adoptively transfer antiviral resistance. We now show that similar depletion of B-cells with rabbit anti-mouse immunoglobulin G plus complement or macrophages by adherence to Sephadex G-10 columns also leaves intact the protective capacity of spleen cells from serum-protected mice. That these results reflect the ability of more than one spleen cell population to transfer antiviral resistance rather than the activity of a non-T, non-B, nonmacrophage cell compartment is supported by the finding that purified splenic T- or B-cells alone from serum-protected DBA/2 mice can adoptively transfer antiviral resistance. Given the previously reported effects of sublethal irradiation on FLV leukemogenesis which could potentially complicate the interpretation of adoptive transfer experiments carried out in this system, analogous studies were performed using a Winn-type assay in which putative effector cells were preincubated with virus before inoculation of the mixture in unirradiated mice. These Winn assay experiments yielded identical results in that serum-protected spleen cells again prevented viral leukemogenesis, and the separate elimination of T-cells, B-cells, or macrophages had no effect on their protective activity. In addition, mixed transfer of serum-protected and normal spleen cells also protected irradiated mice against FLV challenge, providing further evidence that this adoptive protection truly reflects the presence of virus-specific effector cells in the spleens of serum-protected mice and not an inability of these spleen cells to replace radiation-sensitive viral target cells in recipient animals, since these should be supplied by the normal spleen cells in the transferred mixture.

Animals↗
PubMed1981

Allotype suppression induced in the adoptive transfer system: the variables of the system and an apparent absence of a role for T cells.

A study has been made of the variables concerned in allotype suppression of adult spleen cells in the adoptive transfer system. These are; SRBC (antigen) dose; the dose and timing of injection of anti-allotype serum IgG; the number of spleen cells transferred and whether these cells were taken from primed or unprimed donors. Adoptively transferred primed cells are considerably less susceptible to suppression by concomitantly injected anti-allotype serum IgG than are unprimed spleen cells. Injection of anti-allotype serum during the period after adoptive transfer, has shown that primed cells loose their susceptibility sooner (2 days) than the unprimed cells (4 days). Allotype heterozygous CBA spleen cells are less susceptible heterozygous CBA spleen cells are less susceptible to allotype suppression than either allotypically homozygous or heterozygous non-H-2k cells (H-2b,d, or s). Allotype suppression of the TI IgG response to DNP-Ficoll was measured 7 days after adoptive transfer of allotype-homozygous cells from both normal and nude CBA mice (unprimed). The results indicate that T cells do not play a role in the initiation of short-term allotype suppression in the adoptive transfer system.

Animals↗
PubMed1995

Hospital adoption of medical technology: an empirical test of alternative models.

OBJECTIVE: This study examines hospital motivations to acquire new medical technology, an issue of considerable policy relevance: in this case, whether, when, and why hospitals acquire a new capital-intensive medical technology, magnetic resonance imaging equipment (MRI). STUDY DESIGN: We review three common explanations for medical technology adoption: profit maximization, technological preeminence, and clinical excellence, and incorporate them into a composite model, controlling for regulatory differences, market structures, and organizational characteristics. All four models are then tested using Cox regressions. DATA SOURCES: The study is based on an initial sample of 637 hospitals in the continental United States that owned or leased an MRI unit as of 31 December 1988, plus nonadopters. Due to missing data the final sample consisted of 507 hospitals. The data, drawn from two telephone surveys, are supplemented by the AHA Survey, census data, and industry and academic sources. PRINCIPAL FINDING: Statistically, the three individual models account for roughly comparable amounts of variance in past adoption behavior. On the basis of explanatory power and parsimony, however, the technology model is "best." Although the composite model is statistically better than any of the individual models, it does not add much more explanatory power adjusting for the number of variables added. CONCLUSIONS: The composite model identified the importance a hospital attached to being a technological leader, its clinical requirements, and the change in revenues it associated with the adoption of MRI as the major determinants of adoption behavior. We conclude that a hospital's adoption behavior is strongly linked to its strategic orientation.

Capital Expenditures↗
PubMed1988

National Adoption Council Act 1987 (No. 21 of 1987), 18 December 1987.

This Act creates a National Adoption Council in Mauritius with the following objectives: "1) to inquire into all demands for the adoption of citizens by noncitizens before any application is made to the Judge in Chambers; 2) to advise the Minister on all matters relating to demands specified in paragraph 1); 3) to coordinate with overseas official agencies engaged in the adoption and welfare of children." Further provisions of the Act deal with the composition of the Board of the Council, staff, the General Fund of the Council, execution of documents, service of process, and offenses, among other things. The Act also requires all foreign citizens to obtain the approval of the Council before proceeding with the adoption of Mauritian citizens.

Adoption↗
PubMed1977

Schizophrenics' adopting parents. Psychiatric status.

With the exception of one finding in one experiment, adoption studies have demonstrated that genetic and not rearing factors play an etiological role in the schizophrenias. In that one study, clinical evaluations showed the biological parents of schizophrenics as more disturbed than the adopting parents of schizophrenics, who were, in turn, slightly more disturbed than the adopting parents of normal persons. Both the biological and the adopting parents of schizophrenics showed an equivalent degree of Rorschach pathology, suggesting the possible role of a learned communication disorder in the schizophrenic disorders. A replicative study were performed, employing the same design but utilizing a systematic sample. Structured interviews and tests were administered to the biological parents of nongenetic retardates. Structured clinical evaluation showed the biological parents of schizophrenics to be more disturbed than the other two groups, between whom there was no difference in psychopathology. With analysis of the Rorschach tests, the biological parents of schizophrenics showed significantly more Rorschach pathology than found in the other two groups, whose degree of disorder was the same. This study again confirms the role of genetic factors and fails to show an environmental component in the etiology of the schizophrenias.

Adoption↗
PubMed1984

An adoption study of somatoform disorders. III. Cross-fostering analysis and genetic relationship to alcoholism and criminality.

The genetic and environmental antecedents of two clinically distinct somatoform disorders were compared in 859 Swedish women adopted at an early age by nonrelatives. The characteristics of both the biological and adoptive parents of high-frequency "somatizers" were different from those of diversiform somatizers. The risk of diversiform somatization was increased in the adopted-away daughters of men treated for male-limited (type 2) alcoholism, but not in daughters of milieu-limited (type 1) alcoholics. In contrast, the biological fathers of high-frequency somatizers often had a history of recurrent convictions for violent crimes since adolescence, but no treatment for alcoholism. Similarly, alcohol abuse by the adoptive father was associated with increased risk of diversiform but not high-frequency somatization. Thus, high-frequency and diversiform somatization are not only clinically distinct, but also have different genetic and environmental backgrounds. The association of diversiform somatization with male-limited alcoholism, and not with milieu-limited alcoholism, also provides independent support for our earlier distinction between these two types of alcoholism.

Adolescent↗
PubMed1996

Efficient tumor eradication by adoptively transferred cytotoxic T-cell clones in allogeneic hosts.

Tumor-specific cytotoxic T cells (CTLs) can play an important role against cancer as illustrated by the observation that adoptive transfer of tumor-specific CTLs can mediate potent anti-tumor effects. Although such CTLs can be detected at the tumor site, relatively little is known about the mechanisms by which they enter the tumor. In this study, the role of major histocompatibility complex (MHC) class 1 molecules on vascular endothelium in the tumor in entry of, and tumor eradication by, tumor-specific CTL was investigated. Two H-2Db-restricted CTL clones recognizing peptide VNIRNCCYI on human adenovirus type 5 early region 1-(Ad5E1)-induced tumors were used to test whether CTLs were able to cross the vascular endothelium lacking the restricting MHC molecule. One CTL clone recognizes peptide VNIRNCCYI in the context of both H-2Db and H-2Dbm14 molecules. The other CTL clone recognizes this peptide only in the context of H-2Db. Adoptive transfer of these CTLs leads to eradication of Ad5E 1-induced, H-2Db-expressing tumors in B6(H-2Db+) and Bm14(H-2Db-) nude mice. Our data show that presentation of tumor-derived peptides by MHC molecules on endothelial cells of blood vessels in a tumor do not play a major role in eradication of tumors by adoptively transferred CTL in combination with interleukin-2. Moreover, our data show that successful adoptive CTL immunotherapy is possible across allogeneic barriers, without inducing severe side effects, provided the tumor expresses the MHC class 1-peptide complex recognized by the CTLs.

Amino Acid Sequence↗
PubMed1994

Localization of prothymocytes from wild-type and viable motheaten mice following intravenous injection into irradiated adoptive recipients.

Bone marrow cells from viable motheaten (me(v)) mutant mice fail to repopulate the thymus of irradiated recipients upon i.v. adoptive transfer. This defect can be corrected by the addition of wild-type marrow to the me(v)/me(v) marrow prior to i.v. injection. The present study focused on the nature of this apparent defect in me(v)/me(v) prothymocyte activity. We established an adoptive transfer assay system that facilitated the investigation of the migration patterns of wild-type and me(v)/me(v) marrow prothymocytes in adoptive recipients. Wild-type prothymocytes were found to seed the thymus of recipients as early as 1 day after i.v. injection. This early wave of prothymocyte seeding peaked at 4 days and diminished to undetectable levels at 6 days postinjection. After an interval of no detectable wild-type precursor activity in the thymus of primary recipients, a second wave of activity was observed on Day 15. This second wave resulted in permanent engraftment and persisted throughout the observation period. In contrast, only one initial wave of me(v)/me(v) prothymocyte seeding occurred in the recipient thymus. Detection of mev/mev precursors in the recipient's thymus was dependent upon the coinjection of wild-type marrow cells. These results suggest that me(v)/me(v) prothymocytes initially seed to the thymus of adoptive recipients, but fail to proliferate and/or differentiate due to a defect in marrow-derived intrathymic accessory cell activity.

Animals↗
PubMed1997

Th1 CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis.

Cultured cells from Micropolyspora faeni-sensitized donors can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP). To determine whether the CD4+ cells responsible for transfer have characteristics of Th1 or Th2 cells, we established cell lines from lung-associated lymph nodes of M. faeni-sensitized C3H/HeJ mice by culturing with antigen and either IFN-gamma, IL2, and anti-IL4, or IL4. Cell lines were stimulated regularly with antigen, fresh antigen-presenting cells, and the cytokine/anti-cytokine antibody cocktail. At various times after initiation of culture, cells were injected intravenously into recipients, which were then challenged intratracheally with M. faeni and sacrificed and the extent of pulmonary inflammatory response was determined. IFN-gamma, IL4, and IL10 levels were determined in supernatants of cell cultures stimulated with M. faeni to characterize the cell lines as Th1 (IFN-gamma, but low IL4 and IL10 secretion) or Th2 (IL4 and IL10, but low IFN-gamma secretion). Cell lines were differentiated into either Th1 (IFN-gamma = 310 +/- 45 U/ml, IL4 = 0.10 +/- 0.1 U/ml, IL10 = 1750 +/- 75 pg/ ml, >99% CD4+) cell lines by Day 16 of culture or Th2 cell lines (IFN-gamma = 1.8 +/- 1.0 U/ml, IL4 = 830 +/- 388 U/ml, IL10 = 51,700 +/- 10,900 pg/ml, >96% CD4+) by Day 30. Th1 cell lines were able to adoptively transfer EHP whereas Th2 cell lines were unable to adoptively transfer EHP. The ability to transfer EHP was directly related to the amount of IFN-gamma and inversely to the amount of IL4 secreted by antigen-stimulated cells. We conclude that it is possible to produce CD4+ cell lines with either Th1 or Th2 characteristics from lung-associated lymph nodes of mice exposed to M. faeni and that only Th1 CD4+ cell lines can adoptively transfer EHP.

Adoptive Transfer↗
PubMed1997

Treatment of subcutaneous tumor with adoptively transferred T cells.

Adoptive immunotherapy with T cells directed at tumor antigens has been demonstrated to result in the regression of malignant tumors in humans. These encouraging results have prompted the further exploration of parameters necessary to treat tumor in various locations in animal models. We have demonstrated that T cells that are sensitized to tumor antigens and then ex vivo cultured are capable of eradicating pulmonary metastases. In this report, we demonstrate that these T cells are capable of eliminating subcutaneous tumor deposits. Critical to the successful treatment of subcutaneous tumor was treatment with a large number of adoptively transferred T cells and pretreatment of the mice with irradiation. The transfer of T cells from tumor-bearing mice into irradiated mice failed to inhibit the therapeutic effect of ex vivo cultured T cells, suggesting that irradiation was not acting only as an immunosuppressant. Irradiation resulted in increased expression of the F4/80 and 33D1 epitopes on antigen-presenting cells within the tumor. The therapeutic effect of the adoptively transferred T cells was eliminated if either CD4 cells or CD8 cells were depleted. Naive T cells subjected to the same culture conditions were completely ineffective at eliminating tumor. These results demonstrate that adoptively transferred T cells derived from tumor-bearing hosts can treat subcutaneous tumor deposits, and they define the conditions necessary for the elimination of tumor in this location.

Animals↗
PubMed1999

Persistence, immune specificity, and functional ability of murine mutant ras epitope-specific CD4(+) and CD8(+) T lymphocytes following in vivo adoptive transfer.

Adoptive T-cell transfer has been shown to be a potentially effective strategy for cellular immunotherapy in some murine models of disease. However, several issues remain unresolved regarding some of the basic features involved in effective adoptive transfer, such as the influence of specific peptide antigen (Ag) boost after T-cell transfer, the addition of IL-2 post-T-cell transfer, the trafficking of transferred T cells to lymphoid and nonlymphoid tissues, and the functional stability of recoverable CD4(+) and CD8(+) T cells. We investigated several of these parameters, particularly as they relate to the persistence and maintenance of effector functions of murine CD4(+) and/or CD8(+) T lymphocytes after adoptive cellular transfer into partially gamma-irradiated syngeneic hosts. Our laboratory previously identified murine (H-2(d)) immunogenic CD4(+) and CD8(+) T-cell peptide epitopes reflecting codon 12 ras mutations as tumor-specific Ag. Therefore, the model system chosen here employed epitope-specific MHC class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells produced from previously immunized BALB/c mice. Between 2 and 7 days after T-cell transfer, recipient mice received various combinations of peptide boosts and/or IL-2 treatments. At different times after the T-cell transfer, spleen and lung tissues were analyzed phenotypically to monitor the persistence of the immune T cells and functionally (via proliferation or cytotoxicity assays) to assess the maintenance of peptide specificity. The results showed that immune donor T lymphocytes (uncultured immune T cells or cloned T cells) were recoverable from the spleens and lungs of recipient mice after transfer. The recovery of Ag-specific T-cell responses was greatest from recipient mice that received peptide boosts and IL-2 treatment. However, mice that received a peptide boost without IL-2 treatment responded nearly as well, which suggested that including a peptide boost after T-cell transfer was more obligatory than exogenous IL-2 treatment to sustain adoptively transferred T cells in vivo. Ag-specific T-cell responses were weak in mice that either received IL-2 alone or did not receive the cognate peptide boost after T-cell transfer. The T-cell clones were also monitored by flow cytometry or RT-PCR based on expression of the T-cell receptor Vbeta-chain, which was previously characterized. Ag-specific T cells were recovered from both spleens and lungs of recipient mice, demonstrating that the T-cell clones could localize to both lymphoid and nonlymphoid tissues. This study demonstrates that both uncultured and in vitro-cloned T lymphocytes can migrate to lymphoid tissues and nonlymphoid (e.g., lung) tissues in recipient hosts and that their functional activities can be maintained at these sites after transfer, if they are exposed to peptide Ag in vivo.

Adoptive Transfer↗
PubMed1999

MHC-restricted protection of cats against FIV infection by adoptive transfer of immune cells from FIV-vaccinated donors.

The role of cellular immunity in vaccine protection against FIV infection was evaluated using adoptive cell transfer studies. Specific-pathogen-free cats received two adoptive transfers of washed blood cells from either vaccinated or unvaccinated donors with varying MHC compatibility at 1-week intervals, and a homologous FIV(Pet) challenge 1 day after the first adoptive transfer. FIV-specific CTL, IFN-gamma production, and proliferation responses were detected in the PBMC from the vaccinated donors. Seven of eleven (64%) recipients of cells from half-matched/vaccinated donors remained negative for FIV-antibodies after FIV challenge and four of those were completely protected. Two of two recipients of cells from MHC-identical/vaccinated donors were completely protected. All recipients of cells from unrelated/vaccinated, half-matched/unvaccinated, or unrelated/unvaccinated donors were unprotected. Thus, protection mediated by adoptive transfer of immunocytes from vaccinated cats was MHC-restricted, occurred in the absence of antiviral humoral immunity, and correlated with the transfer of cells with FIV-specific CTL and T-helper activities.

Adoptive Transfer↗
PubMed1989

Delta path methods for modeling the effects of multiple selective associations in adoption designs.

In analyses of family data, multiple direct association processes can be modeled by the use of delta path methods derived by Van Eerdewegh (1982), especially the transitivity principle. The method is described for the case of an adoption study involving potential selective matching of adopting parents to two sets of biological parents of adopted offspring in the presence of assortative mating for both wed and unwed couples. Second- and third-order delta paths may be derived by application of the transitivity principle, and these higher-order paths are very convenient in formulating expectations that are due to direct and indirect association processes. Expectations are derived for resemblance among all adults in this three-couple adoption system; examples are given also for deriving parent-offspring expectations to illustrate the general use of higher-order delta paths in structural models of familial resemblance. Matrix notation is employed in order to facilitate the application of the methods in developmental and/or multivariate models.

Adoption↗
PubMed1989

Sex differences in property crime in a Danish adoption cohort.

Sex differences in genetic and environmental influences on criminal behavior against property were studied in a birth cohort of 6129 male and 7065 female Danish adoptees and their biological and adoptive parents. Both genetic and environmental factors were found to contribute to variation in liability to property criminality, the relative proportions of variance explained being similar in males and females. Important shared- and nonshared-family environmental factors were present. In separate analyses of average liability toward property criminality, however, convicted females appeared to be more genetically predisposed than convicted males, a conclusion based on the finding that female property offenders were more likely than male offenders to have convicted biological (but adopted-away) offspring. On the other hand, property-offending males and females did not appear to differ in their average shared-family environmental liabilities, since conviction rates did not differ for adoptees of convicted adoptive mothers and fathers. Also, social class in the adoptive parents of convicted sons and daughters were comparable, further indicating that average shared-family environmental liabilities do not differ between the sexes.

Adoption↗
PubMed1981

Personality resemblance in adoptive families.

Adoption studies provide an opportunity to check on twin-study inferences about genetic and environmental effects on personality. The Texas Adoption Project obtained personality tests and ratings from members of 300 adoptive families: MMPIs and 16PFs for adults, and Cattell scales and parents' ratings for children. Overall there was little personality resemblance among family members, either biologically or adoptively related. Median correlations were typically positive, but under 0.10. Elimination of a rating bias and the use of multiple correlations did not yield notably higher levels of prediction, but restriction to a subsample of well-measured children provided higher correlations and more evidence of heritability, particularly in the extraversion domain.

Adolescent↗
PubMed1992

Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy.

The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2-63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01). The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4. In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes. The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01). In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin. These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification.

Breast Neoplasms↗
PubMed1995

International adoption: a case review of Korean children.

In contrast to the controversial transracial adoption of African American children by Caucasian families in the U.S., international, transracial adoption of Asian children has not received much scientific or societal attention. There has been a steady increase in this unnoticed minority group, made up largely of Korean children. This paper reviews the developmental characteristics of post-adoption adjustments among Korean adoptees and discusses the dynamics of their positive adjustments. Sociopolitical issues of international adoptions are also addressed.

Acculturation↗
PubMed1994

Activation of T lymphocytes for the adoptive immunotherapy of cancer.

BACKGROUND: Adoptive immunotherapy of malignancy involves the passive transfer of antitumor-reactive cells into a host in order to mediate tumor regression. Based on animal models, the transfer of immune lymphoid cells can eradicate widely disseminated tumors and establish long-term systemic immunity. Critical for successful adoptive immunotherapy is the ability to isolate large numbers of immune cells. For clinical therapy, it will require the development on in vitro methods to promote the sensitization and propagation of tumor-reactive cells. However, this is a formidable task since human cancers are postulated to be poorly immunogenic because of their spontaneous origins. RESULTS: Human lymphoid cells for ex vivo activation and subsequent adoptive transfer have been derived from different sources, including peripheral blood, tumor, and lymph nodes. Peripheral blood lymphocytes can be incubated with interleukin 2 to generate lymphokine-activated killer (LAK) cells, which nonspecifically lyse autologous and allogeneic tumor cells in vitro. LAK cell therapy represented the earliest attempt to treat advanced human cancers, with encouraging results documented in patients with renal cell cancer and melanoma. From that experience, the use of more immunologically specific cellular agents with potentially greater therapeutic efficacy has been investigated. One approach uses tumor-infiltrating lymphocytes, which have been characterized experimentally to be more specific in tumor reactivity compared with LAK cells. Other techniques have involved the use of lymphoid cells derived from lymph nodes draining tumors or primed by tumor vaccines. In vitro activation of these cells with tumor antigen or anti-CD3 monoclonal antibody results in the generation of T cells that mediate the rejection of poorly immunogenic tumors in animal studies. These alternate methods are currently being evaluated in clinical studies. CONCLUSIONS: Experimentally, cellular therapy is a potent method to eradicate progressive tumors. Initial clinical studies have demonstrated that this form of therapy is technically feasible and can result in meaningful antitumor responses. Advances in this area will require improved methods to sensitize, isolate, and expand tumor-reactive T cells for adoptive transfer.

Animals↗