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PubMed1980

Detection of early and delayed antitumor effects following curative adoptive chemoimmunotherapy of established leukemia.

Advanced disseminated leukemia can be successfully eradicated by treatment with a combination of noncurative nonlethal chemotherapy plus adoptively transferred immune cells. The time course of tumor elimination following such therapy was examined by bioassay for tumor of peripheral blood and spleen cells from treated mice. Curative treatment with adoptive chemoimmunotherapy did not immediately eliminate all leukemia. Bioassay of cells from treated mice, rather, demonstrated that, following the initial tumor lysis mediated by the chemotherapy and immune cells, a period of tumor regrowth lasting several weeks preceded ultimate tumor eradication. This transient tumor regrowth detectable by bioassay never became clinically evident in the treated mice. However, immunosuppression of mice two weeks after treatment with adoptive chemoimmunotherapy resulted in recurrence of lethal tumor. The results suggest that tumor elimination following curative adoptive chemoimmunotherapy is biphasic and that the efficacy of therapy may be subject to positive and/or negative influences over a prolonged time period.

Animals↗
PubMed1995

Biobehavioral comparisons between adopted and nonadopted rhesus monkey infants.

Differences between adopted and nonadopted infant rhesus monkeys were examined, as were differences between biological and foster mothers, in measures of infancy and postinfancy behaviors, maternal-infant interactions, and neuroendocrine and behavioral responses to separations. Newborns were experimentally allocated to continuous postnatal care by either their biological mothers (n = 9) or adoptive, nonbiological mothers (n = 7). Behavioral observations were completed during the neonatal period, during separations at 30 days and 5 months, and from 6 to 18 months of age, when animals were housed in a large social group. Maternal and infant responses to separation stress were assessed using measures of behavioral, adrenocortical, and growth hormone reactivity. Out of 84 possible comparisons, only six achieved statistical significance, a number compatible with the operation of chance. Negligible differences in behavioral and neuroendocrine endpoints were found between adopted and nonadopted mother-infant pairs. These findings lend additional credence to human studies finding no increase in the incidence or severity of mental disorders in adopted children.

Animals↗
PubMed1995

Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress.

The development of the organism is subjected to critical and complex influences during the perinatal period. Prenatal and postnatal stresses can have different long-term behavioral effects, and appropriate postnatal manipulations can counteract the behavioral effects of prenatal stress. In the present study, we investigated the involvement of changes in the activity of the hypothalamo-pituitary-adrenal (HPA) axis in the long-term effects of prenatal and postnatal events and of interactions between them. We investigated stress-induced corticosterone secretion and hippocampal corticosteroid receptors in male adult rats submitted to prenatal and/or postnatal manipulations. Repeated restraint during the last week of pregnancy was used as prenatal stressor, and adoption at birth was used to change the postnatal environment. We found that (1) prenatal stress prolongs stress-induced corticosterone secretion in adult rats, which was attributed to the observed decrease in central corticosteroid receptors; (2) adoption, irrespective of the stress experience of the foster mother, reverses the effects of prenatal stress; and (3) adoption per se increases maternal behavior and decreases the stress-induced corticosterone secretion peak in the adult offspring. In conclusion, certain prenatal and postnatal manipulations appear to have opposite long-term effects on the activity of the HPA axis, and adoption, probably by modifying maternal behavior, can protect against the effects of prenatal stress. Thus, changes in the activity of the HPA axis may be one of the biological substrates of the long-term effects of certain perinatal events.

Animals↗
PubMed1995

Enhancing physician adoption of practice guidelines. Dissemination of influenza vaccination guideline using a small-group consensus process.

BACKGROUND: A dissemination intervention to facilitate adoption of a preventive practice guideline (influenza vaccination for older adults) in group practices was developed and evaluated. The intervention, small-group consensus process, started with a physician expert presenting the guideline and followed with the group participating in a structured discussion of ways to implement the guideline that culminated in a public commitment (ie, "buy in") to adopt the guideline. METHODS: Thirteen group practices and their primary care physicians (mean size, 5) were assigned randomly to intervention or control arms. In each group practice, physicians in the intervention arm met for 1 hour. Control physicians participated in an unrelated discussion (non-steroidal drug use). Guideline adoption was determined by changes in physicians' vaccination rates that were obtained through prechart and postchart reviews of 51 physicians. Prequestionnaires and postquestionnaires measured influenza knowledge and prevention attitudes. RESULTS: Using analysis of covariance, the small-group consensus process was found to increase physician vaccination rates by 34% compared with the control arm (F (1,48) = 19.49). All intervention arm physicians increased vaccination rates from before to after compared with 54% of control arm physicians. Attitudes and knowledge did not change and were unrelated to increased vaccination rates. CONCLUSIONS: A case is made for the small-group consensus process as an effective utilization-focused dissemination method. Interventions based on group dynamics and sensitive to local practice contexts can be useful in facilitating adoption of guidelines by physicians in group practices.

Decision Making↗
PubMed1994

Evidence for a significant role of CD4+ T cells in adoptive immunity to Listeria monocytogenes in the liver.

Although the ability of CD8+ T cells to adoptively immunize mice against Listeria monocytogenes in the spleen is well established, the role of different T-cell subsets in anti-bacterial protection in the liver, a major target of Listeria infection, remains unclear. Therefore, the ability of sorted CD4+ and CD8+ T cells to adoptively immunize mice against a L. monocytogenes infection in the liver was studied. The results show that positively sorted CD4+ T cells from day 7 Listeria-immune mice were as effective as sorted CD8+ cells in transferring significant anti-Listeria protection in the liver. Similar findings were obtained when CD4+ and CD8+ T cells, negatively selected by antibody-induced complement-mediated depletion in vitro, were used for adoptive transfer. CD8+ T cells, however, were more efficient than CD4+ T cells in transferring protection in the spleen. Taken together, the results show that CD4+ T cells are at least as protective as CD8+ T cells against a L. monocytogenes infection in the liver, thereby arguing against the view that CD4+ T cells are of limited importance in adoptive immunity against listeriosis.

Animals↗
PubMed1977

Communicating through satisfied adopters of female sterilization.

Communication patterns between 127 satisfied adopters of female sterilization (agents) and 257 potential adopters of family planning (recipients) were examined in this study conducted in a rural community in southern India. The influence of satisfied adopters relative to other family planning communication agents was evaluated. Satisfied adopters were identified as the most important source of family planning information by 55 percent of agents and 74 percent of recipients. Communication usually occurred between persons of similar caste, occupation, education, and income.

Communication↗
PubMed2006

Adoptive transfer of TRAIL-expressing natural killer cells prevents recurrence of hepatocellular carcinoma after partial hepatectomy.

BACKGROUND: Antitumor activity of the liver natural killer (NK) cells reportedly decreases after partial hepatectomy, suggesting that patients with such depressed immune status are susceptible to the recurrence of hepatocellular carcinoma (HCC). We hypothesize that adoptive immunotherapy using activated NK cells can be a novel strategy to improve the depressed immune status in patients with HCC after hepatectomy or partial liver transplantation. In the present study, we have tested this hypothesis by using a mouse model. METHODS: Intraportal injection of 1-5 x 10(6) Hepa1-6 cells (hepatoma cell line) did not result in liver metastases in untreated B6 mice, but led to the growth of liver metastases after extensive partial hepatectomy. Utilizing this murine HCC metastasis model, we investigated the antitumor activity of both remnant liver and exogenously transferred NK cells. RESULTS: The anti-HCC activity of liver NK cells significantly decreased after partial hepatectomy. The expression of CD69 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on liver NK cells was temporarily downregulated. The adoptive transfer of NK cells, including a TRAIL-expressing fraction, extracted from the liver perfusates of poly I:C-stimulated B6 mice inhibited the growth of liver metastasis in B6 or (B6xBALB/c) F1 (B6CF1) mice that underwent hepatectomy and received intraportal Hepa1-6 injection. CONCLUSIONS: These findings indicate that adoptive immunotherapy using activated NK cells extracted from normal liver perfusates may be a novel technique for reconstituting the depressed immune status in cases of living donor liver transplantation involving HCC patients, recipients of a partial liver graft.

Adoptive Transfer↗
PubMed1988

In re the Adoption (Amendment) Bill 1987, 26 July 1988.

The President of Ireland referred to the Supreme Court the question whether Section 3 of the Adoption (Amendment) Bill was repugnant to family rights contained in Articles 41 and 42 of the Constitution. Section 3 authorizes a child of parents who were married to each other to be adopted under exceptional circumstances, i.e., when the parents have totally failed their duty to their child, when that failure arises from "physical and moral" reasons and continues for more than a year prior to application, and when such failure constitutes abandonment. The Court found the Bill constitutional. It held that, under Articles 40.3 and 42.5 of the Constitution, the rights of the child within the family could in extraordinary circumstances be supplied by placing a child in an alternative family, and that the preconditions set forth in the Bill were sufficient to protect the constitutional guarantees afforded to the family. After the Supreme Court reached its decision, this Bill was signed into law as the Adoption (Amendment) Act 1988.

Adolescent↗
PubMed1988

Act on rules concerning the acceptance of foreign foster children with a view to adoption, 8 December 1988.

This Act sets forth conditions that must complied with when foreign foster children are accepted with a view to adoption in the Netherlands. A "foreign foster child" is defined as "a minor born outside the Netherlands, who does not have Dutch nationality under Dutch law, and who is, or will be, cared for and brought up in the Netherlands with a view to its adoption, in a family other than the parental family, in such circumstance that the foster parents actually take the place of the parents." The Act does not apply to such fostering not aimed at adoption, which is covered by the directives contained in the 1982 circular on aliens.

Adoption↗
PubMed2000

Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.

OBJECTIVE: To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). DESIGN: Nonrandomized phase 1 clinical trial. SETTING: Academic tertiary care hospital. PATIENTS: Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. INTERVENTION: Patients were vaccinated on the thigh with irradiated autologous tumor cells admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. RESULTS: Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 x 10(9) (range, 1.3 x 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3+ (>97%), being a mixture of CD4+ and CD8+ cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. CONCLUSIONS: Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.

Adult↗
PubMed1996

Romanian adoption. The Manitoba experience.

OBJECTIVE: To study the developmental, behavioral, and medical features in a cohort of Romanian children adopted by Manitoba families. DESIGN: A prospective longitudinal study. SETTING: The Child Development Clinic, Children's Hospital, Winnipeg, Manitoba, from September 1990 to June 1992. PATIENTS: Developmental, behavioral, and medical features were assessed in 22 Romanian children adopted by 18 Manitoba families. RESULTS: Mean (+/- SD) age at adoption was 15.5 +/- 13 months. Mean (+/- SD) age at initial assessment was 19 +/- 12 months and at follow-up, 35 +/- 13 months. Medical complications included 6 children (27%) who were positive for the hepatitis B surface antigen, 5 with intestinal parasites (23%), 1 positive for the human immunodeficiency virus, 1 with rickets (5%), and 1 with monoplegia and cleft palate (5%). Initial growth parameters were less than the fifth percentile for age for head circumference in 10 children (45%), for weight in 8 (36%), and for height in 7 (32%). At follow-up, statistically significant improvement was seen in height and weight. Initial mean (+/- SD) developmental quotients were 82 +/- 20 for gross motor, 83 +/- 23 for fine motor, 83 +/- 19 for cognitive, and 79 +/- 18 for language domains. Follow-up mean developmental quotients improved in all domains (P < .05). Twelve children (55%) displayed abnormal behavior at the initial assessment; behavioral findings persisted in 8 (36%). Initial appropriate activity level and play behavior predicted normal cognitive outcome (P < .05). CONCLUSIONS: This longitudinal study of Romanian adoptees delineates improvements in growth and development once the children are placed in a nurturing environment. The persistence of abnormal behavior in some children underscores the importance of further follow-up.

Adoption↗
PubMed1975

Bias against genetic hypotheses in adoption studies.

Genetic factors are implicated in the cause of psychopathological disorders whenever the incidence of disorder is greater among the adopted-away offspring of affected parents than among those of control (unaffected) parents. The lack of information about most parents who give their children up for adoption could result in the inclusion of a substantial number of high-risk parents in the control groups. This could bias an adoption study against a genetic hypothesis. The Minnesota Multiphasic Personality inventory scores of two groups of pregnant unwed mothers were compared to those of two other groups: married pregnant women and 18-year-old women. Comparisons disclosed that the unwed mothers had significant elevations on five to the nine clinical scales. Elevations on psychopathic deviancy and schizophrenia were particularly substantial. These results indicate a requirement to select control group parents who are representative of the general population.

Adoption↗
PubMed1977

Psychopathology in adopted and nonadopted daughters of alcoholics.

This report completes a series of studies conducted in Denmark comparing drinking patterns and psychopathology in adopted and nonadopted children of alcoholics. Sons of alcoholics had higher rates of alcoholism than controls, whether raised by their alcoholic parents or by foster parents. They did not have more psychopathology otherwise. Daughters of alcoholics, adopted and nonadopted, had a higher rate of alcoholism than was the expected frequency in the general population, but so did controls in the adopted group; neither group had higher rates of other psychopathology, eg, depression. However, daughters of alcoholics raised by their biological parents had significantly more depression.

Adoption↗
PubMed1998

Characteristics of tumor infiltration by adoptively transferred and endogenous natural-killer cells in a syngeneic rat model: implications for the mechanism behind anti-tumor responses.

Interleukin-2-activated, cultured NK cells (A-NK) cells were adoptively transferred into a syngeneic rat liver-tumor model. The kinetics of tumor infiltration by NK cells, originating either from adoptively transferred or from endogenous sources, the localization of these cells in the tumor, and their interactions with extracellular-matrix proteins were studied by immunohistochemistry and transmission-electron microscopy. The adoptive transfer of A-NK cells via the hepatic artery and s.c. injections of IL-2 into rats bearing subcapsularly induced CC531 liver tumors, but also IL-2 monotherapy, resulted in a significant increase of the number of NK cells both at the tumor border and in the tumor center. The majority of tumor-infiltrating NK cells was present in the tumor stroma and only occasionally was an NK cell observed in a tumor nodule in direct contact with tumor cells. Observations by electron microscopy suggested that matrix proteins, abundantly present in the tumor stroma but absent in the tumor nodules, provide a substrate for migration of infiltrating cells, whereas tight structures of matrix proteins surrounding tumor nodules provide a barrier for establishment of direct NK-cell-to-tumor-cell-contact. Our results suggest that direct NK-cell-to-target-cell-contact-mediated lysis is of minor importance for attaining an anti-tumor effect in this model. We hypothesize that treatment of tumor-bearing rats with A-NK cells and/or IL-2 initiates a cascade of events (e.g., secretion of tumor-killing cytokines and/or infiltration of other immune cells) ultimately leading to tumor regression.

Adoptive Transfer↗
PubMed1999

Adoptive immunotherapy prevents prostate cancer in a transgenic animal model.

Cancer-related mortality can be decreased by prevention, early detection and improved therapies. Although animal models should be used to evaluate the success of cancer therapies, their usefulness is controversial. Many cancer therapies that have cured tumors in mice have not met with similar success when attempted in humans. Current animal models rely mainly on inoculating cell lines into animals, a method that does not reproduce the natural development of the tumor, both for the kinetics of induction and the anatomical site concerned. In this study, we have used an SV40 T-antigen-transgenic mouse model of prostate cancer in which the tumor spontaneously develops orthotopically with a disease progression that closely resembles the progression of human prostate cancer. We have used this model to test the suitability of adoptive cellular immunotherapy. Transfer of naive cells obtained from a T-antigen-negative congenic animal had significant but partial effects: it prevented development of malignant tumors, leaving just minor foci of residual tumor and/or hyperplasia. Adoptive transfer of memory lymphocytes specific for T-antigen, which is a prostatic self antigen in this model, prevented tumor development and progression without affecting the morphology and function of involved tissues. Treated animals were able to breed, and their survival was greatly increased. These results strongly suggest that adoptive immunotherapy should be successful in treating early stages of human prostate cancer.

Adenocarcinoma↗
PubMed2000

Tumor size at the time of adoptive transfer determines whether tumor rejection occurs.

Here we investigate the minimal requirements for induction of an anti-tumor response in CD8 T cells in vivo. We compare the efficacy of adoptive transfer of CD8 T cells with a transgenic TCR specific for the main cytotoxic T lymphocyte epitope of the influenza virus nucleoprotein (NP) on the growth of NP-expressing EL4 tumors under different conditions. In a setting in which tumor rejection is solely dependent on tumor-specific CD8 T cells, small immunogenic tumors fail to induce a rejection response, despite the fact that they are not ignored: tumor-specific CD8 T cells are activated, differentiate into effector cells and infiltrate the tumor bed. Nevertheless, tumor rejection does not occur. In sharp contrast, the same immunogenic tumor, when growing as a large tumor mass, is rejected by transferred tumor-specific CD8 T cells. The main features which distinguish the rejection response to a large tumor mass from the response to a small tumor is that, in the latter case, activated CD8 T cells appear much later, and in much smaller numbers. Efficacy of adoptive transfer is thus dictated by the size of the tumor mass at the time of transfer. These findings predict that treatment of minimal residual disease with adoptive transfer will fail, unless vaccination is also provided at the time of transfer.

Adoptive Transfer↗
PubMed2001

Inhibition of tumor metastasis by adoptive transfer of IL-12-activated Valpha14 NKT cells.

A unique lymphocyte lineage, the Valpha14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments. Valpha14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti-tumor immunity. Valpha14 NKT cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo. Here, we report that adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL-2, IL-4, and IFN-gamma, which are cytokines produced by activated Valpha14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL-12-injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL-12-injected RAG-1-/- mice failed to inhibit the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be replaced by adoptive transfer of IL-12-activated Valpha14 NKT cells but not by IL-12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated anti-tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine-mediated immune responses at the effector phase of the Valpha14 NKT cell-mediated anti-tumor activity.

Adoptive Transfer↗
PubMed1993

Adoptive chemoimmunotherapy using ex vivo activated memory T-cells and cyclophosphamide: tumor lysis syndrome of a metastatic soft tissue sarcoma.

Adoptively transferred immune cells in combination with chemotherapeutic agents form the basis for adoptive chemoimmunotherapy (ACIT) of neoplastic disease. Autolymphocytes (ALT-cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor-bearing hosts (TBH) that consist primarily of tumor-specific CD45RO+ (memory) T-cells. These ALT-cells combined with cimetidine (CIM) as autolymphocyte therapy (ALT), have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC). We have previously described an effective ACIT protocol using ALT and cyclophosphamide (CY) for patients with relapsed and refractory non-RCC solid tumors. We now report a case of a patient with a metastatic gastric leiomyosarcoma to the liver, who developed a clinical picture consistent with a tumor-lysis syndrome (TLS), following salvage therapy for his tumor with ACIT using ALT and CY. TLS is a well-known complication resulting from the treatment of rapidly proliferating hematopoietic tumors such as Burkitt's lymphoma and acute lymphocytic leukemia. TLS has also been rarely described in chronic lymphocytic leukemia, as well as certain solid tumors such as breast cancer, small cell lung cancer, and medulloblastoma. However, there have been no previous reports of TLS occurring either secondary to immunotherapy or in sarcomas. The nature of these unusual findings is discussed.

Aged↗