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At least 1,225 records · Page 68Linked to original sources
PubMed1988

Should the mentally ill adopt children? How physicians can influence the decision.

No established criteria exist for determining whether a person with a mental illness should or should not be allowed to adopt children. The basis for opinion in such cases can be derived from previous custody cases described in the literature. The interest of the potential parent, as well as the child, must be a primary consideration. Physicians are often called on to make recommendations regarding the parental fitness of a mentally ill person. An intensive assessment of the potential adoptive parent, including a thorough history and investigation of the person's resources and support systems, is necessary before a recommendation can be made.

Adoption↗
PubMed1997

Adoptive immunotherapy of malignant glioma using tumor-sensitized T lymphocytes.

Malignant glioma remains one disease for which there is no curative therapy. Clearly there is a need to explore new and innovative approaches for their treatment. In this report, we review our preclinical trial of a new adoptive immunotherapy protocol using cytotoxic T lymphocytes (CTL) which had been sensitized to glioma in vivo and then activated and their number expanded ex vivo using compounds which enhance signal transduction. These glioma-sensitized lymphocytes, when introduced systemically into rats with either an intracerebral or intradermal glioma, eradicated or slowed the progression of their tumor. These results indicate for the first time that a reproducible and sustained eradication of a malignant glioma could be achieved by the adoptive transfer of tumor-sensitized, ex vivo expanded CTL. A Phase I clinical trial is now underway to test the safety and potential efficacy of this immunotherapy in patients with recurrent malignant glioma.

Animals↗
PubMedDate not supplied

Submaximal power output in adopted and biological siblings.

Submaximal power output was determined in relative steady state on a bicycle ergometer at a heart rate of 150 beats per minute (PWC150). PWC150 was measured in 880 individuals, 9 to 26 years of age, belonging to 46 sibships of adopted sibs, 66 sibships of unrelated individuals including adoptees, 33 sibships of first-degree cousins, 225 sibships of biological sibs, 56 sibships of DZ twins and 54 sibships of MZ twins. PWC150, PWC150/kg of body weight, PWC150/kg lean body mass, PWC150/cm of height and PWC150/m2 of body surface area were submitted to analysis of variance and correlation analysis after statistical control over age and sex of subjects. Few significant resemblances were found in PWC measurements for adoptive siblings, unrelated sibs and cousins. Sibling resemblance was, however, significant for the sibships of biological sibs, and of DZ and MZ twins. Interclass correlations reached significance only in pairs of biological brothers and sisters, and in pairs of DZ and MZ twins. Estimates of total genetic effect in PWC150/kg in a population of free-living children, adolescents and young adults vary from 0.30 to 0.48. It is concluded that submaximal power output is only moderately affected by the genotype.

Adolescent↗
PubMedDate not supplied

Dental and skeletal maturity in adoptive children: assessments at arrival and after one year in the admitting country.

Seventy-one adoptive children from Asian countries, mainly Korea, were adopted by Danish parents. Height and weight were measured and dental and skeletal maturity assessed immediately after arrival and one year later. Increase in dental age was in complete concordance with the time interval between the two examinations. With regard to skeletal age, the majority of children showed an increased maturation rate although some of the youngest children seemed to be further retarded in maturation rate during their first year in Denmark. Comparison between two methods for assessing skeletal maturity revealed that the 'catch up' observed for children above one year of age was significantly more pronounced when assessed by the TW-2 method than when applying the G-P method. For the Korean children height and weight measurements increased more than the average values for the Danish population.

Adoption↗
PubMed2004

Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty.

BACKGROUND: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. AIM: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. METHODS: Forty-six girls with early or precocious puberty (age < or =9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue. RESULTS: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS). CONCLUSION: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.

Adoption↗
PubMed1999

Growth hormone treatment during suppression of early puberty in adopted girls. Swedish Growth Hormone Advisory Group.

Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotropin-releasing hormone (GnRH) analogues. During such treatment decreased growth velocity is frequent. The aim of this investigation was to study whether the addition of growth hormone (GH) to GnRH analogue treatment improves height velocity and final height in girls with early or precocious puberty. Forty-six girls with early or precocious puberty adopted from developing countries were randomized for treatment with GnRH analogue or a combination of GH and GnRH analogue. After 2 y of treatment the mean growth in the GH/GnRH analogue group was significantly higher, 14.6 cm, compared to 10.9 cm in the control group. The increase in bone age did not differ, while the difference in predicted adult height increased by 2.7 cm in favour of the combination group. Although data on final height are not yet available, combined GH/GnRH analogue treatment for 2 y resulted in a higher growth velocity and predicted final height compared to GnRH analogue treatment alone.

Adoption↗
PubMed2005

Enhancing siRNA effects in T cells for adoptive immunotherapy.

Genetically manipulated T cells can be endowed with novel functions to obtain desired in vivo effects after adoptive transfer. This genetic approach is being used to introduce genes such as chimeric immunoreceptors and tumor-specific T cells are being evaluated in early phase clinic trials. However, the ability to alter the genetic programming of T cells also presents opportunities to remove unwanted T-cell functions in order to augment an anti-tumor effect or endow resistance such as to HIV infection. Specifically, the use of RNA interference (RNAi) to disrupt gene expression by targeting either the mRNA or the promoter, provides investigators with many new opportunities to genetically modify T cells that should prove useful in future applications of adoptive immunotherapy.

Animals↗
PubMedDate not supplied

Merging genetic and environmental effects in the Iowa Adoption Studies: focus on depression.

BACKGROUND: It is generally acknowledged that the vast majority of serious mental disorders have significant genetic contributions that manifest complex inheritance patterns. Despite this, few gene polymorphisms have been unambiguously identified as risk factors for behavioral illness and the mechanisms through which these select polymorphisms affect human behavior is completely unclear. One of the major reasons for this lack of progress is the phenomenon of gene-environment (GxE) interactions. METHODS: We review prior evidence of GxE interactions for major depressive disorder (MDD) in the Iowa Adoption Studies. RESULTS: The results demonstrate the usefulness of these cohorts to direct G effects for MDD. CONCLUSIONS: We conclude that further use of the adoption paradigm will generate critical insight into the effects of candidate genes for a variety of complex human behavioral illnesses.

Adoption↗
PubMed2004

Intracerebral infection with murine cytomegalovirus induces CXCL10 and is restricted by adoptive transfer of splenocytes.

The brain's intrinsic immune system consists of glial cells that produce cytokines and chemokines in response to stimulation with cytomegalovirus (CMV). The present experiments were undertaken to determine whether this intrinsic glial cell response alone is sufficient to control CMV infection of the central nervous system (CNS) or whether effector cells from the somatic immune system are also required. Following stereotactic, intracerebroventricular (icv), injection of murine cytomegalovirus (MCMV) into immunocompetent (C.B-17) mice, viral spread in the brain was limited to the cells of the ventricular walls and the infection was resolved by 10 days post infection (p.i.). In contrast, icv infection of immunodeficient (C.B-17 SCID/bg) mice resulted in viral spread from the ventricles throughout the brain parenchyma and these mice succumbed to lethal disease. Adoptive transfer of total splenocytes from major histocompatibility complex (MHC)-matched, MCMV-primed animals restricted intracerebral viral infection to the periventricular cells and reduced levels of reporter gene expression from the viral genome. Peripheral immune cell transfer also protected immunodeficient animals from lethal disease. Depletion of Thy 1.2(+) cells from MCMV-primed splenocytes abolished the protective effect of adoptive transfer. Viral expression was found to be fourfold greater in the brains of animals given Thy 1.2-depleted splenocytes than from those receiving total undepleted cells. As MCMV infection proceeded in the brains of immunodeficient mice, levels of the T-cell chemoattractants CXCL10 and CCL2 remained elevated, whereas CXCL10 levels waned in the brains of animals receiving transferred splenocytes. Taken together, these results demonstrate the ability of T lymphocytes to restrict intracerebral viral spread and indicate that intrinsic glial cell responses alone are insufficient to control MCMV brain infection.

Animals↗
PubMed2002

Adoptive transfer of Ag-specific T cells to prevent CMV disease after allogeneic stem-cell transplantation.

BACKGROUND: Cytomegalovirus is a major cause of infectious morbidity and mortality after allogeneic stem-cell transplantation (allo-SCT). Farmacotherapy to prevent or treat CMV reaction and infection is only partially effective, and has considerable toxicity. Adoptive transfer of ex vivo generated CMV specific T cells is a new approach to the management of CMV post-allo-SCT. METHODS: A comprehensive review of the published literature describing 1) the recovery of CMV immunity post-allo-SCT and 2) new strategies for the production of CMV specific T cells for adoptive immunotherapy. RESULTS: CMV specific T cells can be generated using a variety of systems comprising different antigen presenting cells and antigens. DISCUSSION: The ability to raise CMV specific T cells on a clinical scale will have a major impact on the management of CMV post-allo-SCT, but will have to be compared to current pharmacological approaches. Further, the raising of CMV specific T cells may serve as a model, to generate other antigen specific T cells including other anti-viral and anti-tumor T cells.

Adoptive Transfer↗
PubMed2003

Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice conditions for clinical adoptive cellular immunotherapy.

BACKGROUND: Adoptive transfer of ex vivo expanded cytotoxic immune cells has become a viable strategy for treatment of malignant disease. Natural killer (NK)-92, a highly cytotoxic, IL2-dependent human NK cell-line, is an excellent candidate as an immunotherapeutic agent, being active for prolonged periods following irradiation and IL2 deprivation, non-toxic and non-immunogenic, and easily expanded. A number of clinical trials using NK-92 for different indications are currently underway. The aim of this study was to develop current good manufacturing practice (cGMP)-compliant expansion methodology for NK-92. METHODS: The ability to expand NK-92 ex vivo was evaluated. Serum-free culture media, as well as media supplements (IL2, serum/plasma/albumin), culture containers and feeding regimens were compared for their ability to support expansion, viability and cytotoxicity of NK-92 cells. RESULTS: NK-92 cells can be expanded in X-Vivo 10 serum-free media with 500 U/mL of rhIL2 (Proleukin), and 2.5% human serum/plasma to achieve concentrations sufficient to treat patients with >5210(10) cells. The protocol involves cultures initiated at 2.5210(5) cells/mL in 25 mL in 1 L Vuelife culture bags, with addition of fresh media plus IL2 every 3 days to maintain an optimal density of NK-92 cells for expansion. Daily disruption of cell aggregates enhances NK-92 cells expansion and viability during the culture period. Final yields of approximately 1.1-1.3210(6) cells/mL in a 1.2 L volume (1.36-1.56210(9) cells; 218-250 fold expansion) over 15-17 days is achievable under cGMP-compliant conditions with >85% viability. The feasibility of this approach has been shown in ongoing clinical trial with NK-92. DISCUSSION: We describe a protocol that allows for >200-fold expansion of NK-92 cells within a 2-2.5 week period under GMP standards, in quality and quantity suitable for clinical adoptive immunotherapy.

Cell Culture Techniques↗
PubMed1991

Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases.

While close contact between lymphokine-activated killer (LAK)/adherent, lymphokine-activated killer (A-LAK) cells and tumor cells is believed to be a prerequisite for initiating the events leading to tumor cell lysis, clear evidence for the ability of these effector cells to infiltrate tumors or tumor metastases in vivo still has to be obtained. In the present study, we report that a significant fraction of adoptively transferred A-LAK cells, labeled with fluorochromes for identification, accumulates in lung and liver metastases of the B16 melanoma, the MCA 102 sarcoma and the Lewis lung carcinoma lines. Thus, 5- to 10-fold higher numbers of A-LAK cells were found in the malignant lesions compared to the surrounding normal tissue. The infiltration seemed very heterogeneous after intravenous injection of moderate numbers of A-LAK cells (15 x 10(6)). However, after adoptive transfer of 45 million A-LAK cells, an A-LAK cell/tumor cell ratio higher than 1:1 in most metastases was observed. Surprisingly, approximately 5% of the lung metastases seemed totally resistant to infiltration even though neighboring metastases were highly infiltrated. While substantial infiltration of lung metastases was seen after i.v. injection, significant infiltration of liver metastases was seen only after intraportal injection of the A-LAK cells indicating impaired traffic of intravenous injected A-LAK cells through the lung capillaries. These results present direct evidence that A-LAK cells, upon a proper route of administration, have the potential to migrate to and heavily infiltrate metastases from murine tumors of different origin.

Animals↗
PubMed1991

Interleukin 7 generates antitumor cytotoxic T lymphocytes against murine sarcomas with efficacy in cellular adoptive immunotherapy.

Interleukin 7 (IL-7) is a 25-kD cytokine that was initially described as a pre-B cell growth factor. This cytokine has also been shown to have T cell proliferative and differentiation effects. In this report, we demonstrate that antitumor cytotoxic T lymphocytes (CTL) generated by secondary in vitro sensitization of draining lymph node cells in IL-7 are effective in treating 3-day syngeneic methylcholanthrene (MCA) sarcoma pulmonary metastases in mice. In vivo titrations comparing IL-7 to IL-2 antitumor CTL show that they have equivalent potency in adoptive immunotherapy. IL-7 antitumor CTL generated against MCA sarcomas of weak immunogeneity are also tumor specific in their in vivo efficacy. This study represents the first successful use of a cytokine other than IL-2 for the generation of cells with in vivo efficacy in cellular adoptive transfer.

Animals↗
PubMed2005

Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers.

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA-peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 x 10(3)/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.

Adoptive Transfer↗
PubMed2000

CD4+ and CD8+ T cells mediate adoptive immunity to aerosol infection of Mycobacterium bovis bacillus Calmette-Guérin.

An adoptive-transfer model using recombinase activation gene-deficient (RAG-1-/-) mice was developed to evaluate CD4+ and CD8+ T cell responses to infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). After receiving immune, unfractionated T cells or T cell subsets isolated by fluorescence-activated cell sorter, the RAG-1-/- mice were exposed to aerosol BCG, and the bacteria load in the infected organs was examined 4 weeks later. Adoptive immunity was expressed more effectively in the spleens than in the lungs. Although CD4+ or unfractionated T cells protected both lungs and spleens, CD8+ T cells conferred significant protection only in the spleens and not in the lungs. The results confirm that in addition to CD4+, CD8+ T cells also play a role in the prevention of bacterial dissemination. This transfer model may be useful for dissecting T cell responses to mycobacterial infection.

Adoptive Transfer↗
PubMed2001

Improvement of HIV-specific immunity in HIV-infected twins treated with highly active antiretroviral therapy, interleukin 2, and syngeneic adoptively transferred cells.

Five HIV-seropositive twins were treated with HAART and given cycles of treatment consisting of adoptive cellular therapy from their HIV-seronegative identical twins followed by a 5-day course of intravenous IL-2. Changes in absolute and percent CD4(+) and CD8(+) cell count were monitored and compared with changes in these parameters occurring in seven age-, sex-, and disease stage-matched HIV-infected patients treated with HAART alone. Increase in the magnitude and breadth of HIV-specific immune responses was monitored in three twin subjects who received multiple treatment cycles. Absolute and percent CD4(+) cell counts rose dramatically and to significantly higher levels in the recipient twins than in control subjects treated with HAART only. The subjects who received multiple cycles of treatment developed new and increased levels of HIV-specific activated and memory cytotoxic T lymphocyte responses, and interferon gamma-secreting effector cells. Treatment consisting of HAART, adoptive cellular therapy, and IL-2 was superior to treatment with HAART alone for improving absolute and percent CD4(+) cell counts and inducing new, or increasing the magnitude of, HIV-specific immune responses in HIV infected patients.

Adult↗
PubMed1998

Role of cytokines in GVL (ESb lymphoma) and GVHD after adoptive transfer of allogeneic T lymphocytes in mice.

ESb lymphoma cells injected i.v. into DBA/2 (H-2d) mice multiply rapidly in the liver and kill all mice in a few days. Adoptive transfer of allogeneic C57B1/6 (H-2b) tumor-immune or normal splenic lymphocytes to sublethally irradiated DBA/2 mice induced a marked antitumor state, graft-versus-leukemia (GVL), increasing the mean survival time 2-3-fold, but also induced an acute and lethal graft-versus host disease (GVHD). We have undertaken experiments to try to dissociate GVL from GVHD. Transfer of immune spleen cells induced a greater GVL than transfer of normal spleen cells with an equivalent to GVHD. Three to five million immune or normal CD8+ T lymphocytes were sufficient to induce both GVL and GVHD. Individual DBA/2 mice were labeled and followed. In mice undergoing GVHD, the spleens were repopulated by donor (H-2b) lymphocytes, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were present in the sera of 26 of 27 and 18 of 20 mice, respectively, together with increased amounts of TNF-alpha and IL-6 mRNA in their spleens. This was in contrast to DBA/2 mice receiving allogeneic cells but not developing GVHD. Both interferon-alpha/beta (IFN-alpha/beta) and IL-12, which had proven very effective in association with adoptive transfer of syngeneic immune T lymphocytes in inhibiting ESb metastases, enhanced GVHD when administered with allogeneic immune or normal spleen cells, and >90% of mice died. Intensive IL-2 treatment inhibited GVHD while maintaining GVL.

Adoptive Transfer↗
PubMed1996

Production of human natural killer cells for adoptive immunotherapy using a computer-controlled stirred-tank bioreactor.

Large-scale ex vivo expansion of human natural killer (NK) cells for adoptive immunotherapy requires assurance of good manufacturing practices. However, maximal expansion of NK is also desired to facilitate clinical trials with large numbers of IL-2-activated NK (ANK). A closed-system stirred-tank bioreactor is amenable to computer control of culture variables, thereby reducing the risk of contamination. We demonstrate that NK cultured in 250-ml spinner flasks expand 2.5-fold more than NK cultured in stationary tissue culture wells. We further show that during 33 days of culture, it is feasible to control the pH between 7.0 and 7.2 and the dissolved oxygen concentration at 40% of air saturation via direct on-line computer control in a 750-ml stirred-tank bioreactor. On-line measurement of optical density by a laser turbidity sensor, as a measure of cell concentration, correlated well with actual cell count data. NK expansion in the 750-ml bioreactor was 7-fold greater than in stationary tissue culture controls and 3-fold greater than in spinner flask controls. Consumption rates of glucose and oxygen and the production rate of lactate were measured and will be used to develop a nutrient feeding strategy to convert the batch reactor experiment into closed-system fed-batch or continuous flow modes. Computer-controlled stirred-tank bioreactors may facilitate clinical trials with high-purity ANK populations for adoptive immunotherapy.

Cell Culture Techniques↗