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PubMed2005

Technological advances in adoptive immunotherapy.

Adoptive immunotherapy is an attractive and elegant strategy for treating a variety of life-threatening diseases. Several approaches have been developed to generate antigen-specific CD4+ and CD8+ T cells for adoptive T-cell therapy in cancer and infectious diseases. Currently, many approaches are based on either the use of autologous peptide pulsed dendritic cells as antigen-presenting cells or nonspecific expansion of T cells. Unfortunately, current approaches lack the ability to serve as reproducible and economically viable methods. Several groups are developing new artificial approaches to overcome problems associated with dendritic cells and the nonspecific expansion of T-cell clones in order to make adoptive immunotherapy more feasible and effective. Thus, by increasing the availability of adoptive immunotherapy, we will be able to better determine the efficacy of the approaches in the treatment of a variety of diseases. In this review, we focus on technological advances that will facilitate adoptive immunotherapy. Specifically, we summarize current strategies which are either based on artificial antigen-presenting cells or on T-cell receptor gene transfer.

Antigen-Presenting Cells↗
PubMed2004

Adopted girls with idiopathic central precocious puberty: observations about character.

The aim of this study was to investigate the psychological traits of adopted girls affected by idiopathic central precocious puberty (ICPP). Twelve adopted girls were evaluated before, during GnRH agonist (GnRHa) treatment, and after the treatment was stopped. Before, during and after treatment, adopted girls with ICPP showed a normal degree of anxiety, an adequate level of maturity, and a correct sexual identification. None of them had symbiotic character traits as previously reported in non-adopted girls with ICPP. The perception of their body was poor before treatment, but improved during GnRHa treatment and psychological support. The changes in the life of adopted girls are so numerous that precocious puberty may represent an additional risk for psychological discomfort. Therefore to treat precocious puberty it may not only be necessary to prevent premature changes in their body but also to give them enough time to face up to their emotional and psychological problems and to become competent adolescents.

Adolescent↗
PubMed2001

Prevalence of infectious diseases among internationally adopted children.

OBJECTIVE: Internationally adopted children are at increased risk of infections acquired in their country of origin. Ongoing surveillance of this unique population is needed to detect changing epidemiology and provide appropriate care. METHODS: We performed a retrospective cohort study of 504 children adopted from abroad and evaluated from 1997 to 1998 to determine the prevalence of and factors associated with various infectious diseases. RESULTS: The mean age of the study participants at medical evaluation was 1.6 years; 71% were girls, and they were adopted from 16 countries, including China (48%), Russia (31%), Southeast Asia (8%), Eastern Europe (8%), and Latin America (5%). Overall, 75 (19%) of 404 children tested had tuberculin skin tests >/=10 mm, but all had normal chest radiographs. BCG vaccination (odds ratio [OR]: 7.37; 95% confidence interval [CI]: 3.29, 17.16) and being Russian born (OR: 2.90; 95% CI: 1.68, 5.00) were risk factors for latent tuberculosis infection. Fourteen (2.8%) children had detectable hepatitis B surface antigen, but no child had active hepatitis C, human immunodeficiency virus, or syphilis. Giardia lamblia antigen was detected in 87 (19%) of 461 tested children, and such children were older (mean: 22 months vs 15.5 months) and more likely to have been born in Eastern Europe (OR: 2.82; 95% CI: 1.70, 4.68). CONCLUSIONS: We demonstrated increased rates of latent tuberculosis infection and G lamblia infection than previously reported. Thus, ongoing surveillance of internationally adopted children, international trends in infectious diseases, and appropriate screening will ensure the long-term health of adopted children as well as their families.

Adoption↗
PubMed2002

Evaluating acceptability and completeness of overseas immunization records of internationally adopted children.

BACKGROUND: Increasing numbers of families in the United States are adopting children who were born in other countries. Appropriate immunization of internationally adopted children provides a challenge to pediatricians who must evaluate documentation of vaccines administered overseas and fulfill the recommended US childhood immunization schedule. The acceptability of vaccinations received outside the United States was addressed by the Advisory Committee on Immunization Practices in 1994, but few population-based studies assessing these vaccinations have been reported. METHODS: We performed a retrospective cohort study of 504 children who were adopted from other countries and evaluated in 1997 and 1998. Our goal was to determine the acceptability of overseas vaccinations for meeting US immunization requirements. We assessed immunization records for both valid documentation of receipt of vaccine and comparability with the recommended US schedule. We also determined the number of children who were up to date (UTD) for diphtheria-tetanus-pertussis, polio, hepatitis B, and measles-mumps-rubella vaccines under the US schedule. RESULTS: The children's mean age at initial US evaluation was 19 months; 71% were girls, and most (88%) had resided in orphanages. They were adopted from 16 countries, most frequently from China (48%) and Russia (31%). Thirty-five percent (178) of children had overseas immunization records, 167 (94%) of which were considered valid. Most children with valid records (112 [67%] of 167) were UTD for 1 or more vaccine series under the US schedule. CONCLUSION: The majority (65%) of internationally adopted children had no written records of overseas immunizations. Among the 178 children with documented overseas immunizations, 167 (94%) had valid records and some vaccine doses that were acceptable and UTD under the US schedule. Additional research and more specific guidance in the most cost-effective approaches to evaluation of overseas vaccinations are needed to ensure appropriate state-side vaccination and to improve the health of these children and their communities.

Adoption↗
PubMed1994

Adoption studies of schizophrenia.

The understanding and treatment of schizophrenia have been greatly hampered by uncertainty about etiological factors and controversy about diagnostic boundaries. Adoption studies have helped clarify both of these problems. First, the adoptees study method, the index offspring of adopting-away schizophrenic biological parents are compared with control adoptees whose adopting-away parents were non-schizophrenic. Earlier studies have found increased illness in the index adoptees, thus supporting a genetic hypothesis. Additionally, in this approach the comparison of index versus control adoptive rearing families permits the assessment of environmental joint or interaction effects. An on-going Finnish study appears to provide evidence supporting both genetic and environmental main effects, as well as joint effects. Secondly, in the adoptees' relatives method, the biological relatives of schizophrenic index adoptees are compared with the biological relatives of non-schizophrenic control adoptees. A Danish study found that the relatives not only have more frequent typical, narrowly defined schizophrenia but also have more 'latent', non-psychotic forms of the illness. Thus, the adoption studies of schizophrenia are proving valuable in establishing the significance of both genetic and environmental contributions to the illness and in clarifying the diagnostic criteria for a genetically relevant syndrome.

Adoption↗
PubMed2001

Immunotherapy of melanoma: a dichotomy in the requirement for IFN-gamma in vaccine-induced antitumor immunity versus adoptive immunotherapy.

The mechanism by which tumors are rejected following the adoptive transfer of tumor-specific T cells is not well characterized. Recent work has challenged the requirement for cytotoxicity mediated by either the perforin/granzyme or Fas/Fas ligand pathway in T cell-mediated tumor regression. Many reports, including ours, suggest that tumor-specific production of IFN-gamma is critical for T cell-mediated tumor regression. However, in most of these studies the evidence to support the role for IFN-gamma is only indirect. We have directly examined the requirement for IFN-gamma using IFN-gamma knockout (GKO) mice. The results show an interesting dichotomy in the requirement for IFN-gamma: Antitumor immunity induced by active-specific immunotherapy (vaccination) required IFN-gamma, whereas adoptive immunotherapy did not. In GKO mice vaccination with the GM-CSF gene-modified B16BL6-D5 tumor (D5-G6) failed to induce protective immunity against parental D5 tumor. However, adoptive transfer of effector T cells from GKO mice cured 100% of GKO mice with established pulmonary metastases and induced long term antitumor immunity and depigmentation of skin. Furthermore, in vivo neutralization of IFN-gamma by mAb treatment or adoptive transfer into IFN-gamma receptor knockout mice failed to block the therapeutic efficacy of effector T cells generated from wild-type or perforin knockout mice. Analysis of regressing metastases revealed similar infiltrates of macrophages and granulocytes in both wild-type and GKO mice. These results indicate that in this adoptive immunotherapy model, neither a direct effect on the tumor nor an indirect effect of IFN-gamma through activation of myeloid or lymphoid cells is critical for therapeutic efficacy.

Animals↗
PubMed2001

Regression of extensive pulmonary metastases in mice by adoptive transfer of antigen-specific CD8(+) CTL reactive against tumor cells expressing a naturally occurring rejection epitope.

In this study, we developed a mouse model of adoptive immunotherapy reflecting immune recognition of syngeneic tumor cells naturally expressing an endogenous rejection Ag. Specifically, in a pulmonary metastases model, we examined the potency and maintenance of an antitumor CD8(+) CTL response in vivo, as well as its effectiveness against an "extensive" tumor burden. The approach taken was to first generate tumor-specific CTL from mice challenged with the CMS4 sarcoma coadministered with anti-CTLA4 mAb, which has been shown to facilitate the induction of Ag-specific T cell responses in vivo. An H-2L(d)-restricted nonamer peptide, derived from an endogenous murine leukemia provirus was identified as a CMS4-reactive CTL epitope based upon the following: CTL cross-recognition of another syngeneic tumor cell line (CT26 colon carcinoma) previously characterized to express that gene product; sensitization of Ag-negative lymphoblasts or P815 targets with the peptide; and by cold target inhibition assays. In vivo, the adoptive transfer of CMS4-reactive CTL (> or =1 x 10(6)) resulted in nearly the complete regression of 3-day established lung metastases. Furthermore, mice that rejected CMS4 following a single adoptive transfer of CTL displayed antitumor activity to a rechallenge 45 days later, not only in the lung, but also at a s.c. distal site. Lastly, the adoptive transfer of CTL to mice harboring extensive pulmonary metastases (> 150 nodules) led to a substantial reduction in tumor burden. Overall, these data suggest that the adoptive transfer of tumor-specific CTL may have therapeutic potential for malignancies that proliferate in or metastasize to the lung.

Abatacept↗
PubMed2004

In vivo cyclophosphamide and IL-2 treatment impedes self-antigen-induced effector CD4 cell tolerization: implications for adoptive immunotherapy.

The development of T cell tolerance directed toward tumor-associated Ags can limit the repertoire of functional tumor-reactive T cells, thus impairing the ability of vaccines to elicit effective antitumor immunity. Adoptive immunotherapy strategies using ex vivo expanded tumor-reactive effector T cells can bypass this problem; however, the susceptibility of effector T cells to undergoing tolerization suggests that tolerance might also negatively impact adoptive immunotherapy. Nonetheless, adoptive immunotherapy strategies can be effective, particularly those utilizing the drug cyclophosphamide (CY) and/or exogenous IL-2. In the current study, we used a TCR-transgenic mouse adoptive transfer system to assess whether CY plus IL-2 treatment rescues effector CD4 cell function in the face of tolerizing Ag (i.e., cognate parenchymal self-Ag). CY plus IL-2 treatment not only enhances proliferation and accumulation of effector CD4 cells, but also preserves the ability of these cells to express the effector cytokine IFN-gamma (and to a lesser extent TNF-alpha) in proportion to the level of parenchymal self-Ag expression. When administered individually, CY but not IL-2 can markedly impede tolerization, although their combination is the most effective. Although effector CD4 cells in CY plus IL-2-treated self-Ag-expressing mice eventually succumb to tolerization, this delay results in an increased level of in situ IFN-gamma expression in cognate Ag-expressing parenchymal tissues as well as death via a mechanism that requires direct parenchymal Ag presentation. These results suggest that one potential mechanism by which CY and IL-2 augment adoptive immunotherapy strategies to treat cancer is by impeding the tolerization of tumor-reactive effector T cells.

Adjuvants, Immunologic↗
PubMed1991

Legal review: access to adoption records--recent developments in case and statutory law.

Recent state court decisions on access to adoption records manifest judicial lack of sympathy toward disclosure of confidential adoption information and a reluctance to abandon earlier precedents. The courts have long frowned upon any action that would potentially discourage or impede the adoption process or that would potentially hurt any of the parties involved. The state legislatures, in response to intense lobbying by adoption groups, have tempered the rigid standards of earlier laws, allowing for the creation of adoption registry services in 21 states and for independent searches for biological parents to solicit their consent in 9 states. Still, only 3 states give an absolute right of inspection, while 18 require a court order before access to records will be allowed. Medical records practitioners should determine the rules applicable to the medical records of adoptees in their states. In the absence of specific court or statutory authority permitting the release of such records or of the consent of the natural parents, practitioners should refuse access to these records.

Adoption↗
PubMedDate not supplied

Risk and protective factors in children adopted from the former Soviet Union.

INTRODUCTION: The former Soviet Union (including the present independent republics of Russia, Ukraine, Latvia, Belarus, Lithuania, and Georgia) is the leading source of children adopted from overseas by persons in the United States (US Department of State, 1998). This study sought to (a) characterize the current social, academic, and conduct competencies of 6- to 9-year-old children adopted from the former Soviet Union who have resided in the United States for at least 2 years and (b) evaluate both risks and protective influences of adoptive families and their relationships to competence via a structural equation model. METHOD: Telephone interviews and a postal survey of children were drawn from a US community sample of 105 children. Measures included (a) Child Behavior Checklist, (b) Teacher Report Form, (c) Vineland Adaptive Behavior Scales, (c) Family Environment Scale, and (d) demographic information. RESULTS: Many children had experienced abuse, abandonment, or neglect between birth and entry to the institution. Their mean birth weight was 2637 g, and alcohol abuse by the birth mother was common (41%). Although the children scored below average in competence, adoptive family environments were positive and served as buffers between the risks experienced by the children and the subsequent development of competence within the adoptive family. CONCLUSION: Children's abilities ranged from severely challenged to developmentally normal. The high rate of fetal alcohol exposure in the children may portend future challenges for families.

Adaptation, Psychological↗
PubMed2000

Environmental transmission of DSM-IV substance use disdorders in adoptive and step families.

BACKGROUND: One factor contributing to the 3- to 5-fold increase in risk for substance use disorders (SUDs) among children of alcoholics may be the rearing environment. These influences may include availability of substances, modeling of SUDs, inadequate parenting, or other factors. The contribution of parental environmental influences on offspring with SUDs may be estimated independently of genetic influences through assessment of adoptees raised by nonbiological parents. METHODS: Relative risk of SUDs was assessed in adult adoptees (N = 442) of alcoholic and nonalcoholic adoptive parents as well as in stepchildren (N = 1859) with alcoholic or nonalcoholic stepfathers who participated in the community-based National Longitudinal Alcohol Epidemiologic Survey (NLAES). RESULTS: Rearing by an alcoholic adoptive mother was associated with increased DSM-IV alcohol abuse. Rearing by an alcoholic adoptive father was predictive of adoptees' illicit drug use, as well as DSM-IV drug dependence. Rearing by an alcoholic stepfather was predictive of stepchild DSM-IV alcohol abuse, illicit drug use, and drug dependence, whereas an alcoholic stepmother was associated with increased illicit drug use in the stepchild. Alcoholism in adoptive parents or step parents did not increase risk for offspring DSM-IV alcohol dependence. In both adoptive and biological families, there was a subadditive interaction of mother by father alcoholism such that the rate of substance abuse when both parents were alcoholic was less than that expected based on the additive effects of each alcoholic parent. CONCLUSIONS: Rearing by an alcoholic parent had a greater influence on alcohol abuse by offspring than on alcohol dependence. The increased risk of proband illicit drug use and drug dependence associated with paternal alcoholism suggested nonspecificity of environmental transmission. Both maternal and paternal cultural transmission effects influenced offspring SUDs.

Adolescent↗
PubMed2001

[International adoption: information guide and medical evaluations].

This article aims to provide a guide to pediatricians attending families involved in international adoptions. Firstly, we describe the pre-adoption consultation, which includes a review of the information available on the child, the immunizations and medications recommended for traveling to the foreign country, and the information concerning the more frequent health problems observed in children adopted from abroad. Secondly, we describe the post-adoption evaluation, which includes a physical examination and the laboratory screening tests recommended for internationally adopted children.

Adoption↗
PubMed1975

Problems after adoption: some guidelines for pediatrician involvement.

Adoptive families face several important parent-child confrontations relevant to the adopted status of the child, for which early intervention is indicated. These postplacement difficulties are often not rooted in psychologic disturbance but rather reflect the problem of information deprivation in adoptive parents. Specifically, confrontations arise out of telling the child of the adoption, the adoptee's need for information about the biologic parents, and the tendency of adoptees to place adoptive parents in competition with the biologic parents. The nature of these problems and guidelines for intervention by the pediatrician are detailed in this paper.

Adolescent↗
PubMedDate not supplied

After adoption: dissolution or permanence?

Results are presented on the whereabouts of 516 adopted children, based on a random sample of children adopted from placement in New York City in 1996. Data from interviews with adoptive parents were augmented by information from adoption subsidy records and state child tracking files, as well as interviews with caregivers of children whose adoptive parents were deceased. There were few dissolutions, but postadoption service needs were many.

Adoption↗
PubMed1992

Adoptive transfer of V beta 2-deleting activity with host cells from mice implanted with C4 preneoplastic hyperplastic alveolar nodules.

Selective deletion of mature peripheral V beta 2+ T-cells was observed in BALB/c mice implanted with the syngeneic C4 preneoplastic hyperplastic alveolar nodule (HAN) but not in mice with sham surgery (W. Z. Wei, R. Ficsor-Jacobs, S. J. Tsai, and R. Pauley, Cancer Res., 51:3331-3333, 1991). We now report the participation of host cells in that process. Peripheral V beta 2+ T-cells were reduced by 50% or more 4 weeks after an i.v. injection of 10 x 10(6) spleen cells from C4 HAN-bearing mice. Both T- and B-cell-enriched splenocytes mediated V beta 2 deletion. Secondary adoptive transfer of splenocytes from the recipients of the primary adoptive transfer also resulted in V beta 2+ T-cell deletion. The splenocytes lose V beta 2-deleting activity after 500 rad irradiation. V beta 2 deletion induced by either C4 HAN or splenocytes was more profound in CD4+ than in CD8+ T-cells. Loss of V beta 2+CD4+ T-cells was observed 5 days after the adoptive transfer of splenocytes, whereas V beta 2+ CD8+ cells were not reduced until day 9 or later. The differential rate of V beta 2+ CD4+ and CD8+ T-cell reduction continued for at least 7 weeks after the adoptive transfer. The pattern of V beta 2 deletion and the sequence of T-cell loss is similar in the recipients of C4 HAN or of adoptively transferred splenocytes. Southern blot analysis demonstrates non-germ line Mtv or MMTV proviral DNA in C4 HAN. Splenocytes of C4 HAN-bearing mice express a higher level of 1.7-kilobase long terminal repeat transcript than normal BALB/c splenocytes, suggesting a role for a unique Mtv/MMTV provirus in V beta 2 deletion.

Animals↗
PubMed2004

The influence of context on the success of adoptive breastfeeding: developing countries and the west.

It is commonly believed that adoptive mothers in developing countries are more successful breastmilk producers than women in the west. A review of published research supports this assertion. However, an examination of the practice of adoptive breastfeeding in developing countries and in the west via the literature reveals differences that may explain the variation in success. Adoptive mothers in developing countries may have greater milk production than mothers in the west because they are more knowledgeable about breastfeeding, practice frequent breastfeeding, remain in close physical contact with their children and live in cultures that are supportive of breastfeeding. They also have reproductive and breastfeeding histories that may make breastfeeding easier, though they are less likely to have pharmaceutical galactagogues available. Adoptive mothers in the west should be encouraged to maximise their milk supply by emulating the mothering styles of women in developing countries and developing a strong support network for breastfeeding. It may be that most adoptive mothers are physically capable of producing sufficient breastmilk for their child but that in the west, sociocultural factors act as preventatives.

Adoption↗
PubMedDate not supplied

The impact of family structure on the adjustment of adopted children.

Psychological and academic adjustments were assessed in a group of 130 adopted children (six to 12 years of age) living in five different family constellations: only children, children with younger adopted siblings only, children with younger biological siblings only, children with older adopted siblings only, and children with older biological siblings only. Few differences were found from one cluster to another, suggesting that family structure, while complicating the dynamics of adoptive family life, plays a minor role in adoption adjustment.

Adaptation, Psychological↗
PubMed1989

Adoption vs. parenting decisions among pregnant adolescents.

The choice of adoption is rare among pregnant adolescents. This exploratory study used regression analyses to ascertain which demographic, social, and intervention variables were related to this decision. The adolescents with mothers who favored adoption and/or had few parenting peer models were more likely to choose adoption. Age, knowledge of peers who had chosen adoption, grades in school, level of involvement in a comprehensive adolescent pregnancy program, and participation in individual therapy or Decision-Making Group were not significantly related to the decision. Decision-Making Group is a once-a-week therapy session that focuses on adoption vs. parenting decisions for pregnant adolescents. Eighty-seven percent of the adolescents who participated in these sessions found them helpful. The policy implications for adolescent pregnancy programs are explored.

Adolescent↗