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A longitudinal study of special-needs adoptive families.

This longitudinal study of special-needs adoptive families assesses change on several measures of adoption outcome. Outcomes were somewhat more negative at the second administration of the survey than at the initial administration, presumably because many of the study children had entered adolescence. On balance, however, the outcomes were still positive at the second administration. Findings support the need for enhanced postadoptive services.

Adolescent↗

Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone.

MoPn-specific T-cell clones were isolated from a T-cell line that was capable of curing chlamydial genital infection by the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) after adoptive transfer. Two clones (designated as 2.14-0 and 2.14-3) were characterized by flow cytometry techniques to be homogenous for L3T4, CD3, and alpha/beta T cell receptor (TcR) T-helper cell markers. The two clones were biovar specific, because they reacted to MoPn but not the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC) or C. trachomatis, serovar type E. Cytokine profile analysis, by a combination of bioassays, ELISA, and slot/Northern blotting for specific cytokine messenger RNAs, further revealed that cultures of antigen-stimulated clone 2.14-0 contained interleukin-2 (IL-2), tumor necrosis factor-alpha, and gamma interferon (a T helper 1 cell [Th1] profile). Clone 2.14-3 was also positive for gamma interferon, a level much lower than that of clone 2.14-0, and negative for IL-4 secretion, suggesting a Th1 profile as well. The ability of these clones to bring about the resolution of the chronic genital chlamydial infection of nude mice was tested by the adoptive transfer of 10(7) cells of each clone into the mice. By 4 weeks after cell transfer of clone 2.14-0, 81% of recipient nude mice (30 of 37) resolved the disease. In contrast, clone 2.14-3 or a control T-cell clone specific for a heterologous antigen were unable to resolve the infection in 20 recipients in each case, even after 100 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cell cycle assessment of adoptive transferred lymphokine activated killer cells.

The use of lymphokine activated killer (LAK) cells for adoptive transfer therapy has been reported from number of clinical trials. To our knowledge, however, there has been no report concerning the cell cycle progression of LAK cells. Thus, for the present study we have attempted to examine the LAK cell cycle either before or after transfer. In vitro and in vivo analyses of LAK cells labeled with bromodeoxyuridine (BrdU) were carried out using two-parameter flow cytometries of their nuclear staining using fluorescein isothiocyanate(FITC)-conjugated anti-BrdU antibody and propidium iodide (PI). The in vitro growth of BrdU-positive cells showed the cells to divide once in the S phase, continue to the G2-M phase and return to the G0-G1 phase with a similar pattern after 48 or 72 h culture. They formed a definite subpopulation and were of phenotypes, thy-1.2 (+), Lyt-1.1 (-), Lyt-2.1 (+), L3T4 (-) and AGM1 (+). The percentage of BrdU-positive cells decreased significantly (P < 0.05) when treated with complement plus anti-thy-1.2, anti-Lyt-2.1 or anti-AGM1 anti-bodies, demonstrating BrdU-labeled LAK cells to have the same phenotype as control LAK cells. As in vitro, the in vivo cell cycle of LAK cells 48 and 72 h after transfer had a similar pattern, and the LAK cells also continued on to the S phase after the first division. The in vivo growth of the LAK cells treated with interleukin-2 (IL-2) was promoted 24 and 48 h after transfer. In conclusion, the present study showed LAK cells to be capable of dividing following transfer and to keep their own phenotypic characteristics; also, that treatment with IL-2 may promote their division. Adoptive transfer therapy seems to be a viable therapeutic method.

Animals↗

Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes.

The immunomodulation determined by natural killer cell activity, delayed-type hypersensitivity to purified protein derivative and phytohemagglutin, and phenotypic changes of peripheral blood lymphocytes was characterized in 12 patients with epithelial ovarian cancer who received adoptive transfer of tumor-infiltrating lymphocytes (TILs) after cisplatin-containing chemotherapy (TIL group). As a control, 10 patients with epithelial ovarian cancer who did not receive infusions of TIL were also examined in the same fashion. In the TIL group, peripheral blood lymphocytes showed increased percentages of cells bearing the CD8 antigen, in contrast to stable percentages of CD4 antigen-bearing cells, resulting in a decreased ratio of CD4+ to CD8+ cells. The percentages of CD16 and CD56 antigen-bearing cells also increased in proportion to augmentation of natural killer cell activity against K562 cells. Additionally, with regard to cell-mediated immunity determined by delayed-type hypersensitivity to phytohemagglutin and purified protein derivative, significantly and slightly enlarged erythema was observed 2 and 8 weeks, respectively, after the injection of TILs (phytohemagglutin, P < 0.05; purified protein derivative, not statistically significant). The control group showed no major changes in any of the immunological markers. These results suggest the possibility that the adoptive transfer of TILs induces immunoactivation of cellular immunity and enhances natural killer activity in patients with epithelial ovarian cancer.

Adult↗

Adoptive transfer of lymphokine-activated killer cells loaded with 4'-deoxy-4'-iododoxorubicin: therapeutic effect in mice bearing lung metastases.

We studied the potential use of lymphokine-activated killer (LAK) cells loaded with 4'-deoxy-4'-iododoxorubicin (IDX) in adoptive immunotherapy experiments. Because LAK cells preferentially locate in the lung, we evaluated the therapeutic effect of IDX-loaded LAK cells in mice bearing lung metastases induced by B16F1 tumor cell injection. In vitro studies showed that LAK cells rapidly incorporated IDX, with maximum uptake at 15 min, followed by a plateau; drug efflux was initially rapid and then continued at a much slower rate. Evaluation of LAK cell cytotoxic activity against relevant target cells showed a 30% decrease after IDX treatment that progressed with time over the next 6 h. P388 tumor cell growth was inhibited by coculture with IDX-loaded LAK cells, thus demonstrating that the released IDX maintained its pharmacological activity. Finally, high performance liquid chromatography analysis of tissue IDX concentration revealed a considerably higher and long-lasting concentration in the lungs of mice receiving IDX-loaded LAK cells, compared to mice given injections of a comparable amount of free drug. Moreover, adoptive transfer of IDX-loaded LAK cells into tumor-bearing mice caused a significant reduction in the number of lung metastases versus control mice given injections of even higher doses of free drug.

Animals↗

Preclinical studies for adoptive immunotherapy in bone marrow transplantation. Generation of anti-CD3 activated cytotoxic T cells from normal donors and autologous bone marrow transplant candidates.

In order to obtain T cells for adoptive immunotherapy after autologous bone marrow transplantation (ABMT) for patients with resistant hematological malignancies, a culture system was developed for growing T cells and inducing non-MHC-restricted cytotoxicity using anti-CD3 monoclonal antibody (OKT3) activation. In this investigation, we show that (1) peripheral blood lymphocytes or bone marrow mononuclear cells (BMMNC) from normal donors and cancer patients can be activated with OKT3 and grown in interleukin-2; (2) normal BMMNC activated with OKT3/IL-2 exhibited non-MHC-restricted cytotoxicity and surface markers comparable to that exhibited by normal PBL activated with OKT3/IL-2; (3) both proliferation and cytotoxic functions were IL-2-dependent; (4) PBL activated with OKT3/IL-2 after cryogenic storage grew and killed comparable to PBL activated with OKT3/IL-2 prior to cryopreservation; (5) OKT3/IL-2-activated PBL and BMMNC obtained from 5 patients with non-Hodgkin's lymphomas (NHL) and 1 patient with acute myelogenous leukemia (AML) increased cell numbers 41-75-fold in 2 weeks of culture; 5 of 6 patients with NHL or AML had PBL and BMMNC that exhibited cytotoxic activity; and (6) contaminating leukemic cells did not overgrow in OKT3/IL-2-activated cultures and could no longer be detected on cytospin specimens after 3 weeks of culture. These data show that T cells in PBL or BMMNC from ABMT candidates can be activated with OKT3/IL-2 for adoptive immunotherapy in combination with ABMT.

Antibodies↗

[Anxiety and unconscious fantasies in adoptive families].

First, after a short introduction, the author goes into the threatened identity in adoptive families and the role sexuality hereby plays. This is demonstrated with a case example. Then the unconscious fantasies and dealing with the incest prohibition are described, followed by thoughts about therapy and the problem of the right time to tell the child about his adoption.

Adolescent↗

Mechanisms of adoptive immunotherapy: improved methods for in vivo tracking of tumor-infiltrating lymphocytes and lymphokine-activated killer cells.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and lymphokine-activated killer cells has been demonstrated to mediate regression of tumors in murine models and in selected patients with advanced cancer. Improved methods for monitoring immune cell traffic, particularly to sites of tumor, are needed to elucidate mechanisms of antitumor activity and optimize treatment protocols. Traditional cell tracking methods such as fluorescent protein labeling and radiolabeling using 111In, 125I, or 51Cr are limited by isotope half-life, leakage or transfer of label from immune cells, and toxicity or altered cell function caused by the labeling process. Labeling with genetic markers allows long-term cell tracking but is laborious to perform and difficult to quantitate. We have used two recently described lipophilic cell tracking compounds (PKH26 and 125I-PKH95) which stably partition into lipid regions of the cell membrane to track immune cells in vivo. Concentrations of each tracking compound which had no adverse effects were determined for a variety of murine TIL and lymphokine-activated killer cell functions. Viability was unimpaired at labeling concentrations of up to 5 microM for PKH95 and 20 microM for PKH26. TIL proliferation was unaltered by labeling with up to 5 microM PKH95, 20 microM PKH26, or a combination of 15 microM PKH26 and 5 microM PKH95. In vivo cytotoxic effector function and in vivo therapeutic efficacy of lymphokine-activated killer cells and TIL were also unimpaired by labeling with 20 microM PKH26 or 1 microM 125I-PKH95. Subsequent studies in an adoptive transfer immunotherapy model used 125I-PKH95 to track the biodistribution of TIL in tumor and in non-tumor-bearing animals and PKH26 fluorescence to monitor microdistribution within tissues and distinguish TIL from host T-cells. The results suggest that differential accumulation, selective retention, or proliferation at the tumor site cannot account for the observed pattern of therapeutic efficacy. We hypothesize that a minimum number of TIL must reach the tumor site in order to achieve a demonstrable therapeutic effect.

Animals↗

Placing an infant for adoption: the experiences of young birthmothers.

This article describes the experiences of 215 young birthmothers who placed their infants for adoption through 30 maternity residences and agencies in 13 states. The prebirth services they received, their immediate postbirth experiences, and several characteristics of their adoption arrangements are described. A bivariate analysis revealed that several service-procedural variables are related to social-psychological outcomes for the birthmothers at six months after the birth. Policy implications are presented.

Adaptation, Psychological↗

[The presence of absent persons: the identification changes of an adopted child].

Through the case study of the analytic psychotherapy of an adopted child, the authors illustrate the specificity of identification problems, in particular towards the paternal imago within an oedipal context. The transferential-countertransferential conditions that enable to consider the psychosexual development, in relation to trauma and adoption, within the framework of the therapeutic relationship will also be considered.

Adoption↗

The family romance fantasies of adopted children.

Despite the absence of psychoanalytic studies to support the position, family romance fantasies have been assumed to be similar in form and function in both the adopted child and the blood kin child. My studies, documented herein from the analyses of three adoptees, reveal that knowing one is adopted results in modifications of the fantasy and that certain types of adoptees seem incapable of effectively creating the paradigmatic family romance fantasy.

Adolescent↗

Genetic approaches to adoptive cellular therapy of malignancy.

The rapid strides made in recombinant gene technology have been the impetus for equally dramatic developments in our understanding of various aspects of cancer biology. These areas include genetic events leading to carcinogenesis, growth factors, cellular proliferation, differentiation, apoptosis, and metastasis. Novel therapeutic approaches that take advantage of this new knowledge involve biological alteration of the host target cell at a genetic level. Many of these approaches are discussed in greater detail in other sections of this issue. This article focuses on genetic approaches to the adoptive immunotherapy of malignancy. This form of cellular therapy refers to the infusion of tumor reactive immune cells to mediate regression of established tumor. This review is divided into several areas, each one involving different methods of genetic manipulation to generate immune cells for subsequent adoptive transfer and include: (1) the use of gene-modified tumors to serve as immunogens to generate antitumor T cells, (2) genetic manipulation of effector cells to enhance antitumor reactivity; and (3) genetic construction of immunocompetent effector cells from naive cells.

Animals↗

[Atypical Plasmodium vivax malaria in an adopted child].

An atypical, because of relatively high parasitemia, multiply-infected erythrocytes and long incubation, Plasmodium vivax malaria case in an foreign born adopted child is presented. Features typical of Plasmodium vivax were enlarged infected erythrocytes, characteristic schizont and Schuffner's dots. Our observation emphasizes the importance of blood smear evaluation in traveller and foreign born adopted children.

Adoption↗

Adoption trends: 1976.

The number of children accepted for adoption by voluntary agencies decreased last year, but the number accepted by public agencies showed an increase. Nonwhite homes approved for adoption continued in short supply.

Adoption↗

[Regional adoptive immunotherapy using activated lymphocytes].

The antitumor effect of PSK was analysed with the "double grafted tumor system" in which BALB/c mice received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by intratumoral administration of 5 mg of PSK. On day 3, one hour after intravenous injection of cyclophosphamide, immunized spleen cells (2 x 10(7) cells/mouse) were injected into the Meth-A tumor. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth-A tumors. However, the intravenous administration of spleen cells showed no antitumor effect. Expansion of peripheral blood lymphocytes was stimulated with immobilized anti CD3 antibody plus IL-2 for use in adoptive immunotherapy. gamma delta T cells proliferated in response to immobilized anti CD3. About 5 x 10(9) BRM-activated killer (BAK) cells were treated in cancer patients who gave their informed consent. One patient with colon cancer and metastatic cancer of the liver was treated with BAK cells by transcatheter arterial infusion without side effect. During the course of BAK treatment, serum IAP CIAE (crossed immunoaffino electrophoresis) pattern of patient changed tumor IAP pattern to normal IAP pattern. Two patients with malignant tumor in maxillary sinus were treated with BAK cells and OK-432 intratumorally. BAK treatment induced more infiltration of T cells, M phi and granulocytes in the tumor than OK-432 treatment alone and showed an antitumor effect with extensive necrosis.

Animals↗

[Adoptive immunotherapy for pancreatic cancer, using MUC1 specific CTL].

A new therapeutic strategy for pancreatic cancer is needed because of its very poor prognosis. We presented the results of adoptive immunotherapy and new adoptive immunotherapy using MUC1 specific CTL. We expect that these new strategies may help improve the prognosis of pancreatic cancer.

Cancer Vaccines↗

Retention of adoptively transferred interleukin-2-activated natural killer cells in tumor tissue.

BACKGROUND: Adoptively transferred interleukin-2 activated natural killer (A-NK) cells are capable of selectively infiltrating tumor, however, only at low efficiency. The aim of this study was to investigate the intratumoral A-NK cell retention using an ex-vivo tissue-isolated tumor preparation. METHODS: R3230AC mammary adenocarcinoma and CSE fibrosarcoma were implanted in the ovarian fat pad of Fisher 344 rats. The tumors were perfused ex vivo 14 to 15 days post-implant with a known number of fluorescent labelled A-NK cells, and the effluent collected serially over time. Non stimulated splenocytes (N-SS) were used as controls. RESULTS: In group 1, tumors were perfused with either A-NK (n = 16) or N-SS (n = 7) cells. The mean number of the cells which remained intratumorally at the completion of the perfusion was 48.37% +/- 14.94 for A-NK cells and 34.68% +/- 13.20 of N-SS (p = 0.048). In group 2, tumors were perfused with a suspension containing both A-NK and N-SS cell (n = 11). The difference in tumor retention between A-NK cells and N-SS was 22.5% (p = 0.0053) for R3230AC tumors (retention of intratumoral A-NK cells was 45.1% +/- 6.47 vs. 22.6% +/- 19.09 for N-SS) and 15.88% (p = 0.028) for the fibrosarcomas (34.01% +/- 15.96 vs. 18.12 +/- 17.78 for A-NK and N-SS, respectively). No difference with respect to retention of A-NK cells or N-SS cells was observed between tumor types (p = 0.23 and p = 0.71, respectively). CONCLUSIONS: The retention of A-NK cells in tumor tissues was significantly better than the retention of N-SS when administered directly. Since the retention of A-NK cells in tumor tissue was high (35-50%), this factor does not explain the low efficiency of adoptively transferred A-NK cells accumulating in tumors when administered systemically.

Adoptive Transfer↗