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PubMed2005

Final height after treatment of early puberty in short adopted girls with gonadotrophin releasing hormone agonist with or without growth hormone.

OBJECTIVE: To compare final height data after treatment with gonadotrophin releasing hormone agonist (GnRHa) alone or in combination with growth hormone (GH) in short adopted girls with early puberty. DESIGN: A randomized controlled trial. PATIENTS AND METHODS: Twenty-six girls with onset of puberty before 10 years of age were treated for 3 years with either GnRHa alone (group A, n = 12) or with GnRHa and GH (group B, n = 14). Mean age at start of treatment was 9.6 years in both groups, bone age was 10.7 (SD 1.1) years in group A and 11.6 (0.8) years in group B. RESULTS: Initial height prediction with average Bayley & Pinneau tables was 149.8 (5.6) and 146.8 (4.8) cm, respectively. Bone age at discontinuation of treatment was 12.3 (0.9) and 13.0 (0.6) years in group A and B, respectively. Height gain defined as the difference between initial height prediction and attained final height, was significantly different between group A and B (5.2 (3.7) and 8.2 (3.4) cm, P < 0.05) using average tables for height prediction. With accelerated tables for prediction the numbers were -1.0 (3.6) and 3.3 (3.5) cm, respectively. At final height, there was no significant difference in height: group A: 155.0 (5.6) cm and group B: 155.0 (5.5) cm. CONCLUSIONS: After 3 years of GnRHa treatment in adopted girls with early puberty, FH is significantly higher than initial height prediction. The addition of GH resulted in a limited further increase in height gain. In the interpretation of the results methodological issues concerning height prediction have to be taken into account.

Adoption↗
PubMed1996

Effect of adoptive transfer of CD4, CD8 and B cells on recovery from MHV3-induced immunodeficiencies.

A chronic viral infection can occur when the host fails to mount an effective immune response to clear the virus. Mouse hepatitis virus type 3 (MHV3) appears to be an excellent model for the study of the relationship between viral-induced immunodeficiency and chronic disease development. (C57BL/6 x A/J)F1 mice surviving acute hepatitis develop a chronic disease characterized by T- and B-cell immunodeficiencies, viral persistence in various organs including the brain, spleen and thymus, and death within 3 months postinfection (p.i.). We have reported that T- or B-cell deficiencies, observed in MHV3 chronically infected (C57BL/6 x A/J)F1 mice, can be partially or totally thwarted by adoptive transfer of CD4+, CD8+ and/or B cells, at 15 days p.i. in mice surviving the acute phase of the disease. Adoptive transfer of syngeneic CD4+ and/or CD8+ allowed a partial restoration of the T-cell deficiencies, as characterized by thymic atrophy, decrease in splenic T cells, and in all thymocyte subpopulations. B-cell immunodeficiency, as defined by a decrease in splenic B cells, as well as in the bone marrow pre-B- and B-cell compartments, and the occurrence of abnormally larger forms of bone marrow pre-B and B cells, were partially thwarted by B-cell treatment only. Splenic B cells and the bone marrow B-cell compartment, respectively, returned partially or totally to normal values, whereas the pre-B-cell compartment remained depleted in infected mice treated with B cells. Levels of all immunoglobulin classes returned to normal values in MHV3 chronically infected mice when treated with CD4+ in combination with CD8+ cells. All T- and/or B-cell treatments, however, were sufficient to thwart the process of the chronic disease, and favoured the survival of mice for up to 6 months p.i.

Animals↗
PubMed2004

Adoptive transfer of dendritic cells from allergic mice induces specific immunoglobulin E antibody in naïve recipients in absence of antigen challenge without altering the T helper 1/T helper 2 balance.

Dendritic cells (DCs) are important in the regulation of immune responses and it has been proposed that these cells play an important role in asthma; however, their role in food allergy is still largely unknown. Our aim was to study specific immunoglobulin E (IgE) and immunoglobulin G (IgG) responses in naïve recipients following adoptive transfer of myeloid DCs from allergic and control mice. The phenotypic features and lymphokine production of DCs were also investigated. CD11c+/hi B220- DCs isolated from spleen and Peyer's patches (PP) of cow's milk (CM) allergic and control mice were transferred intravenously (i.v.) into naïve syngeneic recipients, and IgE- and IgG-specific responses were evaluated. Experiments were also carried out to determine the levels of interferon-gamma (IFN-gamma) and interleukin (IL)-4 produced by splenocytes from naïve recipients following the adoptive transfer, and CD40 ligand (CD40L)-mediated IL-10 production by DCs from allergic and control mice. DCs isolated from spleen and PP of allergic mice, but not control groups, induced CM-specific IgG and IgE antibody production in naïve recipients in the absence of previous immunization, but did not modify the T helper 1 (Th1) and T helper 2 (Th2) balance. Furthermore, although no difference was observed in the expression of canonical DC surface markers, PP DCs from allergic mice produced less IL-10 than DCs from controls. We interpret these data as showing that DCs play a pivotal role in allergen-specific IgE responses and that a Th2-skewed response may not be involved in the early phase of allergic responses. The identification of the mechanisms underlying these events may help to design novel strategies of therapeutic intervention in food allergy.

Adoptive Transfer↗
PubMed1993

Adoptive transfer of low numbers of CD4+ T cells into SCID mice chronically treated with soluble IL-4 receptor does not prevent engraftment of IL-4-producing T cells.

After intravenous injection of 10(5) purified, lymph node (LN)-derived dm2 (H-2d/Ld-) CD4+ T cells into young C.B-17 scid/scid (severe combined immunodeficiency, SCID) mice (H-2d/Ld+), the transplanted Ld-T cells show a selective pattern of engraftment: they repopulate the spleen, the lamina propria of the small intestine and the mesenteric LN (but not other peripheral LN) of the immunodeficient host. CD4+ cells repopulating different lymphoid organs of the SCID recipient mice produce interleukin-2 (IL-2) and interleukin-4 (IL-4) in response to polyclonal stimulation in vitro. Some evidence has recently been provided that cytokines (e.g. IL-4) present at the site of antigen stimulation in vivo decisively influence the pattern of cytokines expressed by T cells activated at these sites. We therefore asked if neutralization of IL-4 by chronic treatment of SCID mice with high doses of recombinant soluble IL-4 receptor (sIL-4R) changes the IL-4 or IL-2 expression pattern of CD4+ T cells adoptively transferred into young SCID recipients. Transplanted SCID mice were chronically treated with two different, recombinant murine sIL-4R proteins. The experimental series further included groups of transplanted SCID mice treated with a recombinant human sIL-4R protein (which does not bind murine IL-4), treated with the anti-murine IL-4 monoclonal antibody (MoAb) 11B11, or non-treated. Transplanted SCID mice treated with the recombinant murine sIL-4R protein preparations displayed detectable sIL-4R serum levels, which demonstrates that the substitution therapy could maintain neutralizing serum levels of anti-IL-4 activity in SCID mice. By contrast, no serum sIL-4R levels were detectable in the sensitive ELISA readout in transplanted SCID mice which were non-treated, treated with the MoAb 11B11, or treated with the recombinant humans sIL-4R protein. The efficiency and the pattern of CD4+ T-cell engraftment, and the lymphokine-producing phenotype of the engrafted dm2 CD4+ cells, was not affected by the continuous IL-4-neutralizing treatment of mice with either the MoAb 11B11 or the soluble IL-4R preparations. Hence, in contrast to the published evidence of the dramatic effect of IL-4 on the lymphokine-producing phenotype of CD4+ T cells stimulated in vitro or in vivo, the chronic suppression in vivo of IL-4 activity (by either different sIL4-R protein constructs, or by the anti-IL-4 MoAb 11B11) did not lead to preferential engraftment of Th1-type CD4+ T cells after adoptive transfer of CD4+ T-cell populations into an immunodeficient recipient.

Animals↗
PubMed1994

Adoptive transfer of cloned T helper cells ameliorates periodontal disease in nude rats.

We have previously described a T helper cell 2-type clone, A3, of rat T cells that provides help for antibody production to Actinobacillus actinomycetemcomitans in vitro and in vivo in normal (euthymic) isogeneic Rowett strain recipient rats. Adoptive transfer of this T helper cell clone to euthymic rats also protects them from periodontal bone loss induced by oral infection with A. actinomycetemcomitans. In the present study, to assess the cell requirement for protection, A3 clone T lymphocytes (10(6)) or naive lymph node (6 x 10(4)) T cells, or A3 plus naive lymph node T cells (6 x 10(4)) were adoptively transferred to groups (n = 7-9) of 30-day-old Rowett athymic nude (rnu/rnu) rats. All recipients were also immunized (intraperitoneally) with 10(7) killed A. actinomycetemcomitans on the day of T cell transfer and orally infected with these bacteria on each of the next 5 days. Recipients of the combined A3+lymph node T cell transfer showed significantly increased serum immunoglobulin G (IgG) and IgM antibody to A. actinomycetemcomitans and in vitro proliferation of spleen lymphocytes to A. actinomycetemcomitans as antigen compared with nude animals receiving lymph node T cells only. Although other possibilities are discussed, we inferred that these differences might be due to successful population of the congenitally athymic rats by A3 clone cells given with a small number of normal autologous naive lymph node T cells. The result of this co-transfer of naive T cells with the A3 clone cells seemed to be greatly increased antibody production and protection from periodontal bone loss.

Aggregatibacter actinomycetemcomitans↗
PubMed1998

Adoptive transfer: the role of perforin in mouse cytotoxic T lymphocyte rejection of human tumor xenografts in vivo.

The popliteal lymph node cells of immunocompetent mice generated a strong in vitro cytotoxic response to footpad injection of several human tumor cell lines and the resulting mouse effector cells predominantly used a perforin-mediated cytotoxic mechanism. A relatively minor FasL-dependent cytotoxic response to CEM-CCRF and Jurkat leukemias, but not colon carcinoma COLO 205 cells, was also detected in immunized perforin-deficient mice. In vitro depletion of CD3+ CD8+ T cells, but not CD4+ T or NK1.1+ cells, completely inhibited lysis of human tumor cells, suggesting that CD3+ CD8+ T cells were effectors of perforin-mediated xenospecific cytotoxicity. Xenospecific cytotoxic T cells from wild-type mice were extremely efficient at rejecting tumor when adoptively transferred into scid mice bearing established COLO 205, CEM-CCRF, or Jurkat tumor xenografts. By contrast, cytotoxic T lymphocytes of perforin-deficient mice had no effect on the growth of established tumor xenografts. These data indicate that perforin, and hence direct cytotoxicity, plays a key role in the ability of adoptively transferred CD8+ cytotoxic T lymphocytes to eradicate established xenografts.

Adoptive Transfer↗
PubMed2005

Blockade of IFN-gamma does not affect the arthritogenicity of T cells generated during the induction of adjuvant arthritis but exacerbates the polyarthritis produced by adoptive transfer of arthritogenic effector cells.

IFN-gamma production is prominent in some models of autoimmune disease, including adjuvant arthritis (AA), but the role of IFN-gamma in the pathogenesis of these diseases is uncertain. Experimental manipulation (administration of cytokine, blocking cytokine action with specific antibody, disruption of genes encoding the cytokine or its receptor) has revealed both pro- and anti-inflammatory effects, depending on the nature of the manipulation and the timing of the treatment. We examined separately the effects of cytokine blockade during the afferent and efferent phases of AA in Dark Agouti rats, using an adoptive transfer system. Effects of IFN-gamma on the efferent phase were investigated by treating recipients with mAb DB-1, which blocks the activity of rat IFN-gamma. When treatment was commenced before cell transfer, the resulting polyarthritis was more severe than in controls treated with normal IgG. Commencing treatment after the adoptively transferred disease had become established caused neither amelioration nor exacerbation, but did cause some delay in resolution. In contrast, treatment of donors did not appear to affect the generation of arthritogenic cells. The main effect of IFN-gamma appears to be modulation of the arthritogenicity of the migratory effector T cells that can transfer AA.

Adoptive Transfer↗
PubMed1998

Adoptive immunotherapy of patients with metastatic renal cell cancer using lymphokine-activated killer cells, interleukin-2 and cyclophosphamide: long-term results.

BACKGROUND: Initial results of adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) appeared to offer promise for treating renal cell cancer (RCC). However, lower response rates were seen in subsequent trials, and the long-term results of this treatment method have not been fully reported. In this study, we examine long-term results of adoptive immunotherapy using LAK cells, IL-2, and cyclophosphamide (LAK/IL-2/CPM therapy). METHODS: We administered 10 courses of therapy to 9 patients with advanced RCC. One patient had liver and para-aortic lymph node metastases; the others had only lung metastases. The clinical effects were initially evaluated 4 weeks after therapy and follow-up was continued for periods of 43 to 76 months. RESULTS: The 4-week evaluation revealed 3 complete responses (CR), 3 partial responses (PR), 1 minor response (MR), 1 patient with no change in disease status (NC), and 2 patients whose disease progressed (PD). One CR patient remained apparently free of disease for 43 months. After tumors recurred in the lung of another CR patient further disease progression was suppressed by IL-2 administration until the patient died from other causes at 46 months. The third CR patient showed tumor recurrence in the lung and was re-treated with the same LAK/CPM/IL-2 therapy. Lung tumors decreased in size (PR), but the patient died due to brain metastasis 2 months after the second round of treatment. The 2 initial PR patients, as well as the MR and NC patients, developed regrowth or new metastatic lesions within 2 to 15 months following therapy. The 2 PD patients died 2 and 9 months after therapy. CONCLUSION: Long-term effects of LAK/IL-2/CPM therapy were not correlated with the maximal response observed 4 weeks after therapy. Although LAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our data suggest that long-term suppression will require surgical removal of remnant tumors or more intensive maintenance therapy.

Adult↗
PubMed2006

A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in North America and Europe.

AIMS: To examine baseline characteristics of patients recruited into ADOPT, a multinational trial comparing three oral glucose-lowering monotherapies. METHODS: Between April 2000 and June 2002, 4360 patients aged 30-75 years with Type 2 diabetes diagnosed for < 3 years and remaining on diet therapy alone with fasting plasma glucose levels (FPG) between 7.0 and 10.0 mmol/l were enrolled by 488 North American and European centres. Medical histories, anthropometric data and laboratory measurements were determined using common methodologies. RESULTS: The mean (SD) age of the patients was 57 (10) years, body mass index 32.2 (6.4) kg/m(2), HbA(1c) 7.4 (0.9)%; 58% were male, 88% Caucasian and 15% smoked. North American Caucasians (NAC) were younger, more obese, and more insulin resistant than European Caucasians (EUC), but had better pancreatic B-cell function. NAC had lower total, low-density lipoprotein- and high-density liporpotein-cholesterol concentrations with higher triglyceride concentrations and were more often on lipid-lowering treatment. They had lower blood pressure levels but were equally likely to be on antihypertensive treatment. Metabolic syndrome was more frequent and microalbuminuria less frequent in NAC. Within North America, NAC had lower HbA(1c) concentrations than Blacks, Hispanics and Asians despite similar or higher FPG and 30-min postchallenge glucose concentrations. CONCLUSIONS: Caucasian North American and European ADOPT patients differ with respect to adiposity, insulin resistance and metabolic syndrome prevalence. North American Blacks, Hispanics and Asians had lower HbA(1c) concentrations than NAC despite similar or higher glucose concentrations. These phenotypic differences may influence the progression of Type 2 diabetes and the response to initial oral glucose-lowering monotherapy.

Adult↗
PubMed1989

Modeling IQ change: evidence from the Texas Adoption Project.

An analysis of genetic and environmental contributions to intellectual change was carried out by means of a path model applied to IQ data from the Texas Adoption Project, an adoption study in which children were measured on 2 occasions approximately 10 years apart. Included in the model were assortative mating, selective placement, genotype-environment correlation, a measure of socioeconomic status, and alternative hypotheses about cross-generation environmental transmission and the persistence of a trait over time. Some form of environmental transmission across generations was necessary, but either of the 2 forms tested was sufficient. The data were best fit by considering persistence over time to occur at the level of the developed trait. The effect of both genes and family environment was significant at the time of the first measurement, but only the genes made an additional contribution between the first and the second, suggesting the necessity of revising some popular stereotypes about development.

Adolescent↗
PubMed1990

Antisocial behaviour and postnatal environment: a French adoption study.

The higher rate of antisocial behaviour in children from lower class environments has been hypothesized as arising from (a) genetic social class differences and/or (b) cultural/environmental disadvantages. The present study aims to evaluate the strength of the incidence of social class on adolescent antisocial behaviour. To separate genetic factors and the prenatal environment from postnatal rearing conditions, 77 children relinquished at birth and adopted before the age of 3 were studied. Using the Rutter "Children's Behaviour Questionnaire for Completion by Teachers", eight antisocial behaviours were assessed when subjects were in late adolescence. With the exception of theft and bullying, results indicate that the higher the adoptive parental social class, the lower the antisocial behaviour rates in the adoptees. It is shown that the relationship between the total score of adoptees' antisocial behaviour and social class cannot be attributed exclusively to a concentration of these behaviours in the lowest class. No significant selective placement was observed. Concordances and discrepancies with previous studies are discussed.

Adolescent↗
PubMed2006

The development of adopted children after institutional care: a follow-up study.

BACKGROUND: Research suggests that institutional care has long-lasting effects on children. However, no study has longitudinally studied infants in an institution and their subsequent development at age four. METHODS: Sixty-one adopted children aged four years who had spent their first two years of life in an institution were compared to 39 children reared in their own two-parent families. Cognitive development, security of attachment, shyness, children's emotional understanding and behavioural problems were examined in both groups. Parental health and stress were also assessed. RESULTS: At four years adopted children still had lower scores on cognitive development, were less secure, and less able to understand emotions than family-reared children. Children with a secure attachment type in infancy were found to be less secure at age four, compared with those who were classified in infancy as having an insecure attachment type. Their physical development had recovered, they were less shy, had no behavioural problems and no problems in the relationship with their teacher. CONCLUSIONS: Early residential group care has long-lasting effects on important socio-emotional and cognitive aspects of preschool children's development.

Adoption↗
PubMed1988

Emotionally disturbed, adopted adolescents: early patterns of family adaptation.

This article focuses on the development of compatibility or goodness-of-fit within adoptive families and on the possible contribution of such problems to emotional disturbance of adolescents. Subjects included 50 adopted adolescents in residential treatment (mean age = 14.96) and their families, and 50 nonadopted adolescents in treatment (mean age = 14.90) and their families. The child, both parents, and the child's caseworker were interviewed. Three distinctive interactional patterns presenting adaptational challenges are discussed: the family's adaptation to the child's hyperactivity, the family's adaptation to the child's avoidance of contact and cuddling from early infancy, and perceived incompatibility between the child's personality and the parents' style. Results are discussed in terms of behavioral and attributional contributions of both the child and parents to the development of compatibility. Implications for clinicians are discussed.

Adolescent↗
PubMed1997

Biology and adoptive cell therapy of Epstein-Barr virus-associated lymphoproliferative disorders in recipients of marrow allografts.

Epstein-Barr virus (EBV) is an ubiquitous herpesvirus which is carried as a latent infection of B lymphocytes and salivary gland epithelial cells in over 90% of normal adults. Latently infected EBV-transformed B cells circulate at low frequency in the blood for the life of the host. These transformed B cells stimulate a heterogeneous and complex host cell response, ultimately leading to the development and maintenance of high frequencies of HLA-restricted T cells specific for the EBV-encoded nuclear antigens EBNA2-EBNA6 and the latency membrane proteins LMP-1 and LMP-2. Responses to latent EBV-encoded proteins are hierarchical with responses to certain epitopes predominating, dependent upon the HLA genotype of the host. Profound suppression of T-cell immunity may permit the emergence of polyclonal, oligoclonal or monoclonal EBV antigen-expressing lymphoproliferative disorders or malignant B-cell lymphomas expressing these latent EBV antigens. Adoptive transfer of small numbers of peripheral blood mononuclear cells or HLA-partially matched T cells from in vitro expanded EBV-specific T-cell lines derived from a seropositive marrow donor has induced durable regressions of bulky, widely metastatic monoclonal EBV lymphomas in a high proportion of cases. This review describes the current state of knowledge and hypothesis regarding the biology and immunology of EBV infection in the normal host, the features of donor, host and virus which contribute to the development of EBV-associated lymphoproliferative diseases and the mechanisms whereby they are controlled by adoptive transfer of immune T cells.

Bone Marrow Transplantation↗
PubMed1994

Adoptive transfer of suppressor T cells induced by Actinobacillus actinomycetemcomitans regulates immune response.

Purified splenic T cells from C3H/HeN mice primed with immunosuppressive fraction (ISF) from A. actinomycetemcomitans were adoptively transferred to syngeneic mice with SRBC. The transfer of splenic T cells from mice, primed with various amounts of ISF for 6 days, resulted in the dose-dependent inhibition of IgM anti-sheep red blood cells (SRBC) plaque-forming cells (PFC) compared with normal and BSA-primed splenic T cells. Furthermore, the transfer of T cells from mice primed with 100 micrograms of ISF for 6 days to syngeneic and CD4-depleted mice caused the highest inhibition. Immune suppression did not depend on the B cell population in spleen from donor mice primed with ISF, nor on haplotypes as recipient. The immunosuppressive function of these ISF-primed T cells was abrogated by 1000 rad irradiation. Splenic T cells from ISF-treated mice could suppress the T cell-dependent proliferative responses of cocultured normal spleen cells in vitro. Analysis of T cell subsets of spleen cells from ISF-treated mice showed that the suppressor cell is susceptible to treatment with anti-CD8 and complement (C). ISF-sensitized suppressor T cells also suppressed secondary IgG anti-SRBC-PFC response after immunization with SRBC in vivo depending on sensitized periods induced by ISF. Treatment of T cells from mice which primed with ISF for 8 days, with goat anti-mouse CD8 antibody and C abrogated their suppressive effects, and secondary IgG response occurred. These results indicate that the adoptive transfer of ISF-induced T cells, which increased suppressor function, caused the perfect blocking of immune response, allowing promotion of secondary infection.

Aggregatibacter actinomycetemcomitans↗
PubMed2006

Mental health issues and the foster care system: an examination of the impact of the Adoption and Safe Families Act.

Although marriage and family therapists are being called on to help at-risk families, some say that clinicians have insufficient knowledge about the impact of policies on families involved in the foster care system. The purpose of this qualitative investigation was to identify how the Adoption and Safe Families Act informs decision making, to recognize trends in decisions regarding termination of parental rights of parents with mental health issues, and to explore treatment issues of families involved in the foster care system. Results indicate that court cases decided after the implementation of the Adoption and Safe Families Act are likely to result in termination of parental rights. Implications for clinicians and researchers are discussed.

Adoption↗
PubMed1977

Sex differences in the expression of adoption ideas: observations of adoptees from birth through latency.

Longitudinal observations of 21 children, 19 of whom are adopted, reveal two consistent patterns---girls manifest greater interest and conflict in relation to adoption than do boys, and interest and conflict are greatest for both sexes during latency. Implications of the findings for the counseling of adoptees and of other children are discussed, and directions for further research suggested.

Adolescent↗
PubMed1987

Support sources of adolescents in families adopting older children.

The social supports of adolescents in families adopting school-aged children are explored. The perception of support provided by parents was related to severity of problems experienced with the new adoptee. Findings suggest that mothers, more than fathers or friends, are pivotal in adolescents' support systems following such adoptions.

Adaptation, Psychological↗