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PubMed1999

Increased severity of Candida vaginitis in BALB/c nu/nu mice versus the parent strain is not abrogated by adoptive transfer of T cell enriched lymphocytes.

The role of the host immune system in combating candidal infections in the vagina is poorly understood. A murine model of Candida vaginitis was used to elucidate the role of T cells in a candidal infection. Athymic BALB/c nu/nu mice or normal BALB/c mice were induced into estrus and then infected with 1 x 10(6) Candida albicans intravaginally. The infection was monitored over 1 week. Samples from blood, small intestine, tongue, kidney, spleen, liver, uterus and vagina were tested for recoverable C. albicans. Histology of the vagina was assessed for both inflammation and extent of infection. Results indicated that the BALB/c nu/nu mice had similar levels of vaginal yeast load to the normal BALB/c mice. In 25-30% of nude mice Candida was also recovered from extra vaginal sites (kidney, liver, small intestine), however, extra vaginal dissemination was not observed in any normal BALB/c animals. Histologically, both the nu/nu and control BALB/c had similar levels of vaginal inflammation; however, the nu/nu mice had more florid fungal growth in the vaginal epithelium. Adoptive transfer of either immune or non-immune BALB/c T cells into nude mice had no affect on either infection or vaginal inflammation. Immunohistochemical staining of vaginal tissues from normal BALB/c mice or nude mice adoptively transferred with either immune or non-immune T cells with anti-CD3 monoclonal antibody revealed no significant difference between groups in the numbers of CD3+ vaginal T cells. However, in mice receiving either immune or non-immune T cells no yeast was recovered from any tissues except the vagina. These data show that T cells have a limited role in protecting the vagina from C. albicans infection.

Animals↗
PubMed2000

The fate of adoptively transferred quiescent encephalitogenic T cells in normal and antigen-tolerized mice.

Adoptive transfer of quiescent encephalitogenic T cells to normal syngeneic recipients was without clinical effect. RT-PCR was used to assess localization of an adoptively transferred quiescent encephalitogenic T cell clone in normal and antigen-unresponsive mice prior to or after challenge with neuroantigen/CFA. The T cell clone was not detectable in lymphoid tissues prior to challenge with neuroantigen; however, following challenge, the clone was found in the spleen, lymph nodes and spinal cord of both normal and antigen-tolerized mice. The latter animals remained clinically normal. Non-activated encephalitogenic T cells transferred to wild-type recipients pretreated i.p. with neuroantigen/IFA were rendered unresponsive. Transfer of the same T cells to alpha/beta T cell-deficient mice pretreated with neuroantigen/IFA resulted in spontaneous disease indicating that an intact alpha/beta T cell system was required for development of the unresponsive state.

Adoptive Transfer↗
PubMed1998

Herpes simplex virus zosteriform lesions with adoptive transfer of immune cells: a murine model which mimics human recurrent disease.

Existing murine models for cutaneous herpes simplex virus type 1 (HSV-1) infection have limited relevance to recurrent disease in humans, since the infection is usually primary rather than reactivated and infection occurs in the absence of an established immune response. To obtain a reproducible model to study the effects of topical antiviral therapy on recurrent disease we have adapted a mouse model which employs zosteriform spread of HSV-1 in the presence of adoptive transfer of immunity (ATI) which mimics human recrudescent lesions. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received adoptive transfer of immune cells from the cervical lymph nodes of syngeneic mice that had been infected in the ear pinna with the same strain of virus 7 days earlier. ATI resulted in a heightened inflammatory response in the target tissues for virus replication. Virus was cleared more quickly from the infected tissues in comparison with mice similarly inoculated without ATI, however, the intensity and duration of the inflammation was greater. The model was then used to test the effect of a topical formulation of foscarnet. The results presented demonstrate that the ATI model can provide useful data concerning the efficacy of topical antiviral chemotherapy in man.

Administration, Topical↗
PubMed1997

Augmentation of cell-mediated immunotherapy against herpes simplex virus by interleukins: comparison of in vivo effects of IL-2 and IL-7 on adoptively transferred T cells.

We investigated the ability of human recombinant interleukin-7 (IL-7) to enhance cytotoxic T lymphocyte (CTL) activity in vivo using mice infected with herpes simplex virus type-1 (HSV-1). IL-7 or interleukin-2 (IL-2) was administered twice daily to immune naive mice subjected to adoptive transfer of immune T cells after infection with HSV-1. The immunotherapeutic effect was measured by detecting the virus recovered from pinna. Administration of HSV-1 immune T cells to naive mice significantly increased their ability to clear the virus. Twice-daily injections of IL-7 at 200 IU provided an additional 20-fold reduction in virus load, compared with T cell therapy alone (P < 0.0005). Combining IL-2 and T cell therapy provided about a sevenfold reduction compared with T cell therapy alone (P < 0.0009). IL-7 also enhanced the antiviral effects of T cell therapy against HSV-1 through the enhancement of CD8+ CTLs, as observed with IL-2. These results indicate that IL-7 may be used adjunct to adoptive T lymphocyte therapy in modulating human viral diseases and cancer through enhanced immune T cell activities.

Adjuvants, Immunologic↗
PubMed2003

Stress relief after infertility treatment--spontaneous conception, adoption and psychological counselling.

OBJECTIVE: In this study, we sought to evaluate characteristics of couples with spontaneous conceptions after treatment with assisted reproductive technologies (ART). STUDY DESIGN: Data from 254 couples who underwent 1127 therapy cycles between November 1987 and February 1997, were analyzed. Chi-Square (chi(2)) test and Student's t-test were used. P<0.05 was considered significant. RESULTS: Spontaneous pregnancies occurred in 14% of all treated couples. Psychological counselling only was performed in 21% but was observed significantly more frequently among patients without later spontaneous conception. Ten percent of all treated couples applied for adoption. The miscarriage rate was significantly higher in the group of treatment dependent pregnancies compared to the group of patients with later spontaneous conception (27% versus 9%). The spontaneous conception rate differed significantly depending on women's age and normal semen analysis. CONCLUSION: Appearance of spontaneous conception after ART-procedures should be taken into account in the first patient's interview. Depending on women's age and andrological parameters, treatment-success will differ. The positive impact of psychological counselling for stress relief during and after therapy should also be noted, even though a statistically significant impact could not be demonstrated in the present study. Adoption should be discussed as an alternative to overcome infertility.

Abortion, Spontaneous↗
PubMed2002

Functional evaluation of ex vivo expanded cord blood lymphocytes: possible use for adoptive cellular immunotherapy.

OBJECTIVE: To examine the possibility of adoptive cellular immunotherapy such as donor lymphocyte infusion using ex vivo expanded cord blood (CBL) lymphocytes, the potential expansion ability of CBL lymphocytes and the function of expanded CBL lymphocytes were evaluated. MATERIALS AND METHODS: Mononuclear cell fractions derived from CBL or peripheral blood (PBL) were placed in anti-CD3 monoclonal antibody-coated flasks and cultured in the presence of recombinant human interleukin-2 for 4 days. Cells then were transferred to noncoated flasks and cultured for another 2 weeks. On day 14, polyclonality, cell surface markers, killer activity, and intracellular cytokine profiles were evaluated. RESULTS: Cells were polyclonally expanded. The differences in cumulative fold expansion on day 14 between CBL [1174 +/- 637 (292-1939), n = 6] and PBL [1247 +/- 568 (517-2328), n = 9] were not significant (p = 0.95). Phenotypic patterns of both expanded CBL and PBL were similar. CD4/CD8 ratio of expanded CBL appeared to remain greater than 1 on day 8. In contrast, that of expanded PBL became less than 1. In both cases, approximately 20% of cells had the CD3(+)CD8(+)CD56(+) phenotype. At an effector to target ratio (E/T) of 40:1, the natural killer activity of expanded CBL (64.5% +/- 10.8%, n = 9) was significantly higher than that of expanded PBL (48.3% +/- 16.8%, n = 9) (p < 0.01, Mann-Whitney U-test). However, there was no significant difference in lymphokine-activated killer activity between expanded CBL (45.3% +/- 25.2%, n = 7) and expanded PBL (67.2% +/- 12.3%, n = 7). Interferon-gamma-producing cells were dominant in both cases. CONCLUSIONS: It was feasible to achieve approximately 1000-fold expansion of CBL, and the phenotype and function of expanded CBLs were essentially equivalent to those of expanded PBL. This suggested that ex vivo expanded CBL may be applied to adoptive cellular immunotherapy such as donor lymphocyte infusion.

Antibodies, Monoclonal↗
PubMed1987

Porencephaly and schizencephaly in adopted infants. Frequency ascertainment in a risk group.

A formal inquiry on the health state of 1206 legally adopted children from Indonesia revealed cerebral palsy in 9 (0.9% of 1029 responses obtained), including two who had died. CT examination performed in 7 cases was abnormal in all. Four types of lesions were seen: 1. Bilateral full thickness porencephalies (BFTP lesion) in 4 cases, amounting to 0.4% of the total population on which response was obtained. 2. Full thickness porencephaly of the area of one internal carotid artery in 1 case. 3. Schizencephaly-like lesion in 1 case, confirmed by magnetic resonance imaging. 4. Supratentorial midline cyst resulting in hydrocephalus. The frequency of the BFTP lesion found in 4 out of 7 cerebral palsied investigated by CT is remarkable in view of its rarity in radiological studies on cerebral palsy and because of its relationship to prenatal rather than perinatal damage according to previous pathological studies. This is the first systematic study on the neurodevelopmental outcome of a group of adopted babies which indicates an increased risk to specific prenatal brain damage.

Adoption↗
PubMed2003

A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT).

OBJECTIVES: The Atrial Dynamic Overdrive Pacing Trial (ADOPT) was a single blind, randomized, controlled study to evaluate the efficacy and safety of the atrial fibrillation (AF) Suppression Algorithm (St. Jude Medical Cardiac Rhythm Management Division, Sylmar, California) in patients with sick sinus syndrome and AF. BACKGROUND: This algorithm increases the pacing rate when the native rhythm emerges and periodically reduces the rate to search for intrinsic atrial activity. METHODS: Symptomatic AF burden (percentage of days during which symptomatic AF occurred) was the primary end point. Patients underwent pacemaker implantation, were randomized to DDDR with the algorithm on (treatment) or off (control), and were followed for six months. RESULTS: Baseline characteristics and antiarrhythmic drugs used were similar in both groups. The percentage of atrial pacing was higher in the treatment group (92.9% vs. 67.9%, p < 0.0001). The AF Suppression Algorithm reduced symptomatic AF burden by 25% (2.50% control vs. 1.87% treatment). Atrial fibrillation burden decreased progressively in both groups but was lower in the treatment group at each follow-up visit (one, three, and six months) (p = 0.005). Quality of life scores improved in both groups. The mean number of AF episodes (4.3 +/- 11.5 control vs. 3.2 +/- 8.6 treatment); total hospitalizations (17 control vs. 15 treatment); and incidence of complications, adverse events, and deaths were not statistically different between groups. CONCLUSIONS: The ADOPT demonstrated that overdrive atrial pacing with the AF Suppression Algorithm decreased symptomatic AF burden significantly in patients with sick sinus syndrome and AF. The decrease in relative AF burden was substantial (25%), although the absolute difference was small (2.50% control vs. 1.87% treatment).

Aged↗
PubMed2000

Winter birth and biological family history in adopted schizophrenics.

To investigate relationships between birth season and biological family history in schizophrenia, this study used a sample of schizophrenics that had the advantages of (a) particularly thorough diagnostic assessments of schizophrenics' relatives, including information from direct interviews as well as chart reviews, and (b) schizophrenic probands who were adopted at early age, mitigating the usual confounding of genetic and postnatal environmental influences of the family. Adopted schizophrenics with no biological family history of schizophrenia-spectrum disorders were significantly more likely to be born in winter months than were either (a) their own biological relatives, including their sibs and half-sibs, (b) schizophrenics with a positive family history for schizophrenia-spectrum disorders, or (c) people in the general population. Family-history-positive schizophrenics and their schizophrenic relatives were, in turn, significantly less likely than their own non-schizophrenic biological relatives to be born in the winter; schizophrenics in these families tended to be born in the milder-weather seasons, particularly the spring and fall. Results suggest that environmental factors associated with winter birth may be etiologically important in schizophrenia, particularly for cases in which familial liability factors are weak. By contrast, a familial, probably genetic, liability factor may be especially important in schizophrenics born in mild weather.

Adoption↗
PubMed1997

Prospects for adoptive T cell therapy.

Since the establishment of methods to isolate genes encoding cytotoxic T lymphocyte defined tumor antigens, several antigens have been identified and characterized for suitability as target antigens for immunotherapy. The development of innovative strategies to generate T cells targeting these antigens and lessons learned from clinical trials of adoptive immunotherapy of viral diseases should facilitate the design of clinical trials for specific adoptive immunotherapy of cancer.

Antigens, Neoplasm↗
PubMedDate not supplied

Treatment of refractory recurrent malignant glioma with adoptive cellular immunotherapy: a case report.

We report the successful treatment of a patient with recurrent malignant glioma with adoptive cellular immunotherapy. The patient is a young adult with recurrent progressive disease refractory to aggressive multi-modality therapy including repetitive surgical resection, radiation, radiosurgery and chemotherapy. He received multiple courses of local administration of autologous lymphokine-activated killer (LAK) cells in combination with a low dose of interleukin-2 (IL-2) through an Ommaya reservoir-catheter system. The side-effects of this treatment were limited and manageable. The patient achieved a complete remission, as demonstrated by MRI and confirmed by glucose-positron emission tomography (PET) imaging 11 months after initiation of immune therapy. Twenty-six months later, the patient is still in remission with improving performance status. Adoptive cellular immunotherapy utilizing autologous LAK cells with low dose IL-2 appears to be a safe and effective therapy for a subset of patients with primary, recurrent or progressive malignant glioma following conventional therapy.

Adult↗
PubMed2000

Eradication of established tumors by CD8+ T cell adoptive immunotherapy.

We generated the DUC18 T cell receptor transgenic mouse expressing an H-2Kd -restricted transgenic T cell receptor specific for the syngeneic CMS5 fibrosarcoma rejection antigen mutated ERK2(136-144). DUC18 mice were capable of specifically eliminating lethal CMS5 tumor challenges, and transfer of DUC18 splenocytes to naive nontransgenic recipients conferred protection from subsequent and established CMS5 tumor burdens. Eradication of established tumor burdens by adoptive transfer of DUC18 splenocytes was dose and time dependent. Transferred tumor-specific T cells remained functional in vivo and capable of rejecting small tumors even in the presence of large, established tumor burdens. These findings highlight the kinetic battle between tumor growth and the production of a tumor-specific response and have critical implications for effective adoptive immunotherapy.

Animals↗
PubMed1998

Induction of differentiation in maxillary adenoid cystic carcinomas by adoptive immunotherapy in combination with chemoradiotherapy.

The successful treatment results of a case of maxillary adenoid cystic carcinoma (ACC) and the possibility of differentiation of ACC cells with chemoradioimmunotherapy are described. Combined therapy was applied to two maxillary ACCs. Adoptive immunotherapy consisted of intra-arterial injection of lymphokine-activated killer cells (total 9.0 x 10(8) cells) and recombinant interleukin-2 (1.8 x 10(5) U) and interferon-gamma (1.8 x 10(5) U) was combined with 60Co radiation (50 Gy), 5-fluorouracil (4000 mg) and peplomycin (10 mg). Immunohistochemical staining of the biopsy material obtained during the therapy revealed a marked decrease of proliferating cell nuclear antigen-positive cells and a prominent increase of Lewis Y antigen- and bone morphogenetic protein-2-positive cells. The disappearance of tumour cells and the remodeling of the sinus wall with calcification in the sinus cavity, which had been occupied by the tumour, were observed after therapy in both patients. Adoptive immunotherapy in combination with chemoradiotherapy is useful for the treatment of ACC.

Aged↗
PubMed2000

International adoption of institutionally reared children: research and policy.

This article summarizes the research on the developmental outcomes of postinstitutionalized children and discusses the implications for social policy. Postinstitutionalized children often reach their adoptive families with varying degrees of physical growth retardation, cognitive delays, and socioemotional problems. Many children demonstrate remarkable recovery following adoption. Unfortunately, some of the children continue to display significant problems that require professional intervention. It appears that the children's recovery may be influenced by their early experiences with their birth family and in institutional care, and there is suggestive evidence that postadoption experiences also play a role. These findings indicate that preadoption and postadoption services may support the outcome of postinstitutionalized children.

Adoption↗
PubMed1998

Augmentation of the antitumor effect of adoptive immunotherapy by in vivo sensitization of EL-4 lymphoma and pre-treatment with sizofiran.

The antitumor effects of adoptive immunotherapy using LAK cells treated with sizofiran (SPG) following in vivo antigen sensitization with EL-4 lymphoma (EsLAK), comparing nonsensitized LAK cells (sLAK), were studied in mice with intraperitoneal implantation of EL-4 lymphoma. EL-4 cells treated with Mitomycin C (100 micrograms/ml) were introduced by inoculation into the peritoneum of C57BL/6 mice for antigen sensitization. Four days later, SPG (100 micrograms) was intramuscularly injected. Three days after SPG administration, mononuclear cells obtained from the spleen were prepared for LAK cells (EsLAK). The following results were obtained: 1) The survival period was significantly greater in the sLAK and EsLAK groups than in the control group. The survival period in the EsLAK group was significantly greater than that in the sLAK group. 2) The number of EL-4 cells in the peritoneal exudate cells 11 days postimplantation was lowest in the EsLAK group, and the number of lymphocytes including LGL was largest in the EsLAK group, compared with the sLAK group and the control group. 3) The EsLAK cells showed significantly more enhanced cytotoxic activity against EL-4 than the sLAK cells. 4) Histopathological findings of metastatic lesions of the liver and spleen stained by HE 11 days postimplantation showed less infiltrating tumor cells and more lymphocytic infiltrations in the sLAK and EsLAK groups compared with the control group. These results suggest that induction of LAK cells by administration of SPG to lymphocytes treated by in vivo sensitization with tumor antigen increases the efficacy of adoptive immunotherapy.

Adjuvants, Immunologic↗
PubMed1998

The use of BRM-activated killer cells in adoptive immunotherapy: a pilot study with nine advanced cancer patients.

Adoptive immunotherapy using MHC-nonrestricted-lymphocytes, peripheral blood gammadelta T cells and NK cells was devised. Peripheral blood mononuclear cells (3 x 10(7)) were selected by immobilization to anti-CD3 monoclonal antibody for 4 days and cultured for 2 weeks in the presence of IL-2. Thereafter they were reactivated by 500 U/ml of IFN-alpha and 1000 U/ml of IL-2 for 1 hour. Enhancement of NK and LAK activities was confirmed. Peripheral blood gammadelta T cells proliferated in response to immobilized anti-CD3 antibody (3% to 30%). Approximately 6 x 10(9) BRM-activated killer (BAK) cells composed of CD56+ gammadelta T cells and CD56+ NK cells, were dispensed to cancer patients via intravenous drip infusion. Nine patients were treated with BAK cells every 2 weeks or every month on an outpatient basis. During the course of adoptive immunotherapy, the crossed affinity immunoelectrophoresis (CAIE) pattern of serum immunosuppressive acidic protein (IAP) was analysed. Both the production and glycosylation pattern of IAP is changed in response to tumor enlargement and may therefore act as a marker of the disease progression. During the course of BAK therapy, the glycosylation IAP pattern of 6 patients changed from tumor (T) to normal (N). In addition, the performance status of all patients was maintained at 90-100% of the Karnofsky scale and any side effects including fever were not observed during treatments with BAK cells. Moreover, the overall quality of life (QOL) of the patients, scored at the Face scale was favorable. In addition, blood levels of activated gammadelta T cells producing IFN-gamma were assayed as an indication marker of BAK therapy. The normal range of IFN-gamma producing gammadelta T cells comprised 6.9 +/- 0.9% of peripheral blood mononuclear cells (PBMC), according to a single cell FACScan analyses of PBMCs derived from normal individuals. IFN-gamma producing gammadelta T cells of Patients No. 8 and 9, who received extensive chemotherapy before initiation of BAK therapy, comprised only 0.2% and 2% of PBMC, respectively. These patients died 3 and 6 months after beginning BAK therapy. Peripheral blood gammadelta T cells of Patients Nos. 1-7 proliferated in response to immobilized anti-CD3 antibody and the frequency of IFN-gamma producing gammadelta T cells in PBMC preparation of these patients were over 3% before initiation of BAK therapy. Since our data show a positive correlation between survival time and initial gammadelta T cell counts, a low frequency of these cells may contraindicate BAK therapy.

Adult↗
PubMed2003

Institutionalization, behavior and international adoption: predictors of behavior problems.

Since the mid-1990s, over 10,0000 children have immigrated to the United States annually via international adoption. These children bring to their families unique strengths, as well as the possibility, for some, of physical, emotional and behavioral health risks, and challenges. This article presents predictive models on behavioral health problems for one group of international adoptees from Romania (n = 216). It is a companion piece to an earlier article that described behavior issues and compared the international adoptees to a group of children adopted through the public child welfare system using a cross-sectional approach. This article illustrates that a history of institutionalization had minimal long-term adverse effects on a child's behavioral health. The parent-child relationship was a strong resource for parents at both time periods. However, there was a strong relationship between parental negative reports with the relationship and child behavior problems.

Adoption↗
PubMed1998

Multivariate path analysis of specific cognitive abilities data at 12 years of age in the Colorado Adoption Project.

A parent-offspring multivariate conditional path model was fitted to specific cognitive abilities data from the Colorado Adoption Project (CAP) when the offspring were 12 years of age. The sample included 175 adoptees, 175 sets of adoptive parents, 175 biological mothers, 34 biological fathers, and 209 nonadopted children and their parents. Consistent with results obtained from multivariate genetic analyses of CAP data obtained at earlier ages, the effects of familial environmental transmission on individual differences in specific cognitive abilities were not significant. Assuming complete isomorphism (i.e., that the genetic and environmental etiologies of individual differences are the same) between the child and the adult measures, the heritability estimates for verbal, spatial, perceptual speed, and visual memory were .26, .35, .38, and .53, respectively. Although the heritability estimate for visual memory is somewhat higher than those for verbal, spatial, and perceptual speed abilities, these estimates are not significantly different. These estimates are higher than those obtained when the adoptees and controls were 4 years old (Rice et al., 1986, 1989); thus, heritabilities of specific cognitive abilities may increase as a function of cognitive development. Alternatively, genetic stability from childhood to adulthood may be greater from 12 years than from 4 years, which would be interpreted as greater heritability by the CAP parent-offspring design. The genetic correlations among the four measures were substantial, ranging from .27 between verbal and spatial abilities to .78 between spatial ability and perceptual speed. However, differences among these correlations are not significant, suggesting that their covariation may be due to general cognitive ability. Finally, estimates of bivariate-heritability indicate that on average about half of the phenotypic correlations among the four specific cognitive ability measures are due to genetic effects.

Adoption↗