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Cultural socialization in families with internationally adopted children.

Cultural socialization attitudes, beliefs, and parenting behaviors were examined in families with internationally adopted children. The authors hypothesized that parents with lower color-blind racial attitudes would be more likely to engage in enculturation and racialization parenting behaviors because they hold stronger beliefs in the value and importance of cultural socialization. Using data from the Minnesota International Adoption Project, the results support this mediation model of cultural socialization. Individual variations in cultural socialization also are discussed in terms of child development and shifting adoption attitudes and practices.

Acculturation↗

Informal adoption among black adolescent mothers.

While adolescent decision-making about adoption and parenting is an area of growing concern for researchers, few studies have been made of informal adoption. This paper examines the practice of informal adoption as a response to out-of-wedlock pregnancy among 54 black urban adolescent females.

Adaptation, Psychological↗

The family life cycle in adoptive families.

An approach to the study of adoption based on a family life cycle perspective is presented, emphasizing the special nature of the adoptive family. The changing tasks of such families and of adopted individuals are outlined in a developmental sequence, illustrated with vignettes, that is intended as a guide for clinical intervention.

Adolescent↗

Achieving openness in adoption: some critical issues in policy formulation.

Despite some recent attitudinal and legislative changes, release of adoption information is largely limited and conditional. This paper identifies several issues inherent in the sealed records controversy and argues that cohesive policy formulation depends on systematic examination of the views of those most directly affected. Findings of a three-year study of adoptees, adoptive parents, birth parents, and adoption agency workers are presented.

Adolescent↗

Psychopathology in adopted and nonadopted children: a clinical sample.

The relationships of adoptive status to presenting psychopathology and to demographic and psychosocial variables were examined in a large sample of children and adolescents who attended psychiatric outpatient services over a 14-year period. Adopted boys and girls were both at increased risk of disruptive behavior, including conduct disorders and ADHD. Age at time of adoption was not related to psychopathology.

Adolescent↗

Increased intensity lymphodepletion and adoptive immunotherapy--how far can we go?

In a recent clinical trial involving patients with metastatic melanoma, immunosuppressive conditioning with fludarabine and cyclophosphamide resulted in a 50% response rate in robust long-term persistence of adoptively transferred T cells. Experimental findings indicate that lymphodepletion prior to adoptive transfer of tumor-specific T lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T cells and competing elements of the immune system ('cytokine sinks'). Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. Here we review recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning. We also address safety issues associated with translating experimental animal results of total lymphoid ablation into clinical practice.

Animals↗

Adoptive tumor therapy with T lymphocytes enriched through an IFN-gamma capture assay.

Successful adoptive T-cell therapy has been demonstrated in viral disease and selected forms of cancer. However, it is limited by the difficulty to efficiently isolate and amplify autologous tumor-reactive T-cell clones. Tetramers of major histocompatibility complex (MHC) class I and peptide have facilitated the characterization of CD8+ T cells specific for tumor-associated antigens. However, for adoptive T-cell therapy, MHC-tetramers have limitations: they require knowledge of tumor antigens, which is often not available; they select T cells with a single specificity, thereby posing risk for selection of tumor escape variants; they do not select for function, so that T cells may be anergic when isolated from cancer patients; and they do not allow the isolation of CD4+ T cells that can be essential for tumor rejection. Because interferon (IFN)-gamma is essential for tumor rejection, we isolated live T cells based on their IFN-gamma production. IFN-gamma secreted by previously activated T cells is retained on the cell surface, allowing their specific isolation and expansion. We show here that IFN-gamma+ but not IFN-gamma- T cells from tumor-immunized mice are cytolytic and mediate tumor rejection upon adoptive transfer. Importantly, tumor-specific T cells can be enriched from lymphocytes infiltrating human renal cell carcinoma by the IFN-gamma capture assay.

Animals↗

Adoptive immunotherapy for cancer: building on success.

Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the use of vaccines, haematopoietic-stem-cell transplantation, modified preconditioning regimens, and alternative methods for the generation and selection of the T cells to be transferred.

Animals↗

A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2.

Most B-cell malignancies are incurable diseases and therefore warrant new therapeutic approaches. In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination. Autologous tumour-specific T cells for adoptive T-cell transfer were propagated in vitro by repetitive stimulation with autologous ex vivo CD40-activated PCL cells. CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants. Autologous T cells (5 x 108 and 2.5 x 109 for two separate treatment cycles) generated ex vivo and cytotoxic against autologous tumours were infused and well tolerated by the patient. Fever and myalgias were closely related to IL-2 injections and no other adverse effects were observed. A temporary decrease of PCL cells in peripheral blood was seen after the first cycle of adoptive T-cell therapy, tumour cell vaccination and low-dose IL-2. Tumour progression was associated with tumour cells that (1) expressed a complex karyotype, (2) demonstrated loss of MHC class II, and (3) did not induce autologous tumour-specific T-cell lines ex vivo. We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.

Adoptive Transfer↗

Gammadelta T cells assist alphabeta T cells in the adoptive transfer of contact hypersensitivity to para-phenylenediamine.

Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2.5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2.5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1(+), B220(+), alphabeta TCR(-), gammadelta TCR(-), CD3(-), CD4(-), CD5(+) and CD8(-). The in vitro treatment of effector cells with MoAbs against not only alphabeta TCR but also gammadelta TCR, together with complement, was found to diminish substantially the late response, elicited 12-24 h after challenge. Gammadelta T cells reconstituted the ability of alphabeta T cells to transfer 24 h CHS responsiveness. The phenotype of the gammadelta T cells that assist CHS effector alphabeta T cells was CD3(+), CD4(-) and CD8(+) and these regulatory gammadelta T cells were neither Ag-specific nor MHC-restricted. Furthermore, gammadelta T cells from normal spleen could also assist alphabeta T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that alphabeta T cells strongly expressed mRNA IFN-gamma, whereas gammadelta T cells expressed not only IFN-gamma but also IL-4 and IL-10. These data indicate that not only early response cells and alphabeta T cells but also Th2 type gammadelta T cells may play an important role in the elicitation of CHS to PPD.

Adoptive Transfer↗

New arrivals: speech and language assessment for internationally adopted infants and toddlers within the first months home.

Speech-language pathologists are increasingly requested to assess development in newly arrived internationally adopted children. These infants and toddlers typically arrive home with developmental delays and a lack of proficiency in any language, making it difficult to make objective service delivery decisions. This article reports the results of speech and language assessments for a group of 28 children aged 12 to 24 months who were newly adopted from Eastern Europe. Most of the children did well, with average English language standard scores within normal limits on the Communication and Symbolic Behavior Scale-Developmental Profile. The majority of children were also rapidly learning to understand and produce English words as measured on the MacArthur-Bates Communicative Development Inventory. These findings were used to develop peer-based infant-toddler guidelines for early speech and language intervention. Using these guidelines, 65% of the internationally adopted children did not require early intervention, 7% were borderline and recommended for follow-up assessments within 2 to 3 months, and 28% were recommended for speech and language early intervention.

Adoption↗

Starting over: a preliminary study of early lexical and syntactic development in internationally adopted preschoolers.

To explore early language acquisition in internationally adopted preschoolers, we collected parental reports (CDI-2) and speech samples from 14 children adopted from China between the ages of 2 years, 7 months and 5 years, 1 month. Their lexical and syntactic development was qualitatively similar to infants acquiring English as a first language: nouns and social words dominated early vocabularies; verbs and closed-class items became more frequent as vocabulary size increased; and lexical and syntactic development were tightly correlated. This research has several implications for clinicians. First, it demonstrates that parental reports provide valid information during the first year after adoption and could be useful in identifying preschool children in need of further assessment. Nine to 15 months after arrival many children reached the ceiling of the CDI-2, suggesting that this instrument has limited utility after the first year. Finally, the rapid lexical and syntactic growth of these children suggests that many of them may eventually catch up with their native-born peers.

Acculturation↗

Medical evaluation of internationally adopted children.

BACKGROUND: Despite many reports of medical illness in children adopted from abroad, there are currently no accepted guidelines for medical evaluation of this population. METHODS: Two hundred ninety-three children adopted from 15 countries (mean age, 14.0 months; 55 percent girls) were evaluated by history taking, physical examination, and screening tests for hepatitis B virus (HBV), human immunodeficiency virus type 1, tuberculin reactivity, intestinal parasites, syphilis, excretion of cytomegalovirus, renal disease, and anemia. All but four were seen within one month of their arrival in the United States. RESULTS: Fifty-seven percent of the children (168 of 293) were found to have at least one important medical condition. Eighty-one percent of the diagnoses were established by screening test, rather than by history taking or physical examination. Infectious diseases made up the majority of the medical conditions (73 percent). Serologic testing for hepatitis B surface antigen was positive in 5 percent of the children. Characteristics associated with the acquisition of HBV infection included arrival within the first three years of the study (P = 0.017), Asian origin (P = 0.011), and receipt of a blood transfusion abroad (P = 0.008). Ten children (3 percent) had positive Mantoux skin tests, and four of these had active pulmonary tuberculosis. Tuberculin reactivity was significantly associated with older age (P less than 0.001) and lower weight (P = 0.037). Intestinal parasites were isolated from 14 percent of the international adoptees. Non-Korean adoptees were 16 times more likely to be harboring at least one intestinal parasite than were Korean adoptees (P = 0.005). CONCLUSIONS: Directed screening tests should be a routine component of the medical evaluation of all children adopted from abroad, regardless of age, sex, or country of origin.

Adoption↗

Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells.

Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without the in vivo constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety, in vivo persistence, and efficacy of adoptively transferred CD8+ T cell clones targeting the tumor-associated antigens, MART1MelanA and gp100 for the treatment of patients with metastatic melanoma. Four infusions of autologous T cell clones were administered, the first without IL-2 and subsequent infusions with low-dose IL-2 (at 0.25, 0.50, and 1.0 x 10(6) unitsm(2) twice daily for the second, third, and fourth infusions, respectively). Forty-three infusions of MART1MelanA-specific or gp100-specific CD8+ T cell clones were administered to 10 patients. No serious toxicity was observed. We demonstrate that the adoptively transferred T cell clones persist in vivo in response to low-dose IL-2, preferentially localize to tumor sites and mediate an antigen-specific immune response characterized by the elimination of antigen-positive tumor cells, regression of individual metastases, and minor, mixed or stable responses in 8 of 10 patients with refractory, metastatic disease for up to 21 mo.

Adult↗

Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy.

The conventional approach to cytotoxic T-lymphocyte (CTL) induction uses maximal antigen concentration with the intent of eliciting more CTL. However, the efficacy of this approach has not been systematically explored with regard to the quality of the CTLs elicited or their in vivo functionality. Here, we show that a diametrically opposite approach elicits CTLs that are much more effective at clearing virus. CTLs specific for a defined peptide epitope were selectively expanded with various concentrations of peptide antigen. CTLs generated with exceedingly low-dose peptide lysed targets sensitized with > 100-fold less peptide than CTLs generated with high-dose peptide. Differences in expression of T-cell antigen receptors or a number of other accessory molecules did not account for the functional differences. Further, high-avidity CTLs adoptively transferred into severe combined immunodeficient mice were 100- to 1000-fold more effective at viral clearance than the low-avidity CTLs, despite the fact that all CTL lines lysed virus-infected targets in vitro. Thus, the quality of CTLs is as important as the quantity of CTLs for adoptive immunotherapy, and the ability to kill virally infected targets in vitro is not predictive of in vivo efficacy, whereas the determinant density requirement described here is predictive. Application of these principles may be critical in developing effective adoptive cellular immunotherapy for viral infections and cancer.

Amino Acid Sequence↗

The effects of children on parents: adoptee genetic dispositions and adoptive parent psychopathology.

Although the traditional focus in socialization research has been on the effect of parents on their children (Finley, 1999), recently, researchers have turned their attention to the effects of children on their parents (Ambert, 1992; Demick, Bursik, & Dibiase, 1993). An important confound in the study of the effects of children on parents, however, is shared genetic or biological heritage. One method of avoiding this confound is for researchers to study adoptees and adoptive parents who have no shared genetic heritage. We, therefore, designed the present secondary analysis to examine the effects of adopted children on their adoptive parents without confounding shared biological heritage.

Adoption↗

Controversial attachments: the indirect treatment of fostered and adopted children via Parent Co-Therapy.

Fostered and adopted children often show a large array of psychosocial problems and are conceptualized as having attachment disorders. It can be necessary to engage such children in direct mental health treatment, in addition to interventions set up to deal with their problems through agencies such as Education and Social Services. In order to protect children from a multitude of treating professionals, thereby potentially further weakening the emerging parental attachments, a model is proposed of indirect treatment of children, with the adoptive parents as co-therapists. This elevates the status of parents and is controversial in child mental health work as it challenges traditional hierarchies. We refer to this model, based on a single case study, as Parent Co-Therapy (PCT). It is proposed that this may be a suitable treatment model for fostered and adopted children, particularly in the early years of placement. The model has the potential to strengthen the children's attachments to the parents and vice versa, with a concomitant reduction in symptomatology.

Adoption↗

Fate and function of anti-CD3/CD28-activated T cells following adoptive transfer: IL-2 promotes development of anti-tumor memory T cells in vivo.

BACKGROUND: Adoptive immunotherapy with T cells activated through CD3 alone requires exogenous IL-2 for T-cell function and survival after transfer, but the in vivo cytokine requirement of T cells activated through CD3 and CD28 is unknown. We hypothesized that CD3/CD28-activated T cells, unlike those activated through CD3 alone, might develop into long-lived memory T cells, either with or without systemic IL-2. METHODS: We used MHC class I-restricted TCR transgenic T cells from the OT-1 mouse, specific for the surrogate tumor Ag ovalbumin (OVA), to assess the trafficking kinetics, antigenic responsiveness and anti-tumor efficacy of dual-activated T cells in vivo as a function of IL-2 administration. At days 7, 14, and 28 after transfer, lymph node cells and splenocytes were examined for donor cell persistence and antigenic responsiveness by FACS and ELISA, respectively. RESULTS: In IL-2-treated mice, donor CD8+ T cells persisted and developed a memory phenotype, based on CD44 and Ly6c expression at day 28, while mice given no IL-2 had fewer donor cells at all time points. OVA-specific release of IFN-gamma was higher from lymphocytes of IL-2-treated mice compared with no-IL-2 mice (P<0.02 at all time points). In mice challenged with an OVA-bearing subline of the AML leukemia model C1498, IL-2 did not confer added protection from tumor challenge at 1 or 2 weeks after adoptive transfer, but gave improved survival at 4 weeks post-transfer. DISCUSSION: We conclude that exogenous IL-2 is not required for anti-tumor activity of CD3/CD28-activated CD8+ cells early after adoptive transfer, but promotes T-cell persistence that confers disease protection at more remote times.

Acute Disease↗