Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that human umbilical cord blood contains stem/progenitor cells comparable in number to that of adult bone marrow. We report here the first successful cases of transplantation of umbilical cord blood cells. The patients were suffering from Fanconi's anemia, complicated by severe aplastic anemia. During pregnancy, it was shown that the mother was carrying a sibling unaffected by the disease and with HLA identical to the patient. Cord blood was collected and frozen in liquid nitrogen at birth. After conditioning with low-dose cyclophosphamide (20 mg/kg) and thoraco-abdominal irradiation (5 grays), the patients received a cord blood transplant of thawed cells. Three patients have been transplanted without any immediate side-effect. One has not enough follow-up, but two patients are alive and well with complete donor hematologic reconstitution and no chronic graft versus host disease. Potential developments of this technique are an extension of applicability with regard to other diseases that might be transplanted and whether such transplants can be performed in adults. The relative immaturity of the lymphoid system at birth may be advantageous in decreasing the graft versus host reaction if these cells are used in a mismatched transplantation. Cord blood cell banks may be useful for transplants in patients lacking an HLA-identical donor.
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PMID:Transplantation of umbilical cord blood in Fanconi's anemia. 198 24

Many questions are raised in this review about the role of adult donor granulocyte transfusions in the setting of overwhelming bacterial neonatal sepsis. There clearly exists a number of variables, which influence the survival and morbidity associated with bacterial sepsis. The important differences in these studies highlight the need for prospective large multicenter studies to definitely clarify these issues. Important criteria, which are yet to be established and which impact significantly, include the time of administration of adjuvant granulocytes, the number of granulocytes that need to be harvested, which group of neonates require early granulocyte transfusions, the best method for optimal and easy granulocyte collection, the frequency and intervals of granulocyte transfusions, and improved methods for the early identification of neonatal candidates who would benefit from the granulocyte transfusions. The benefits of granulocyte transfusions (ie, the improvement in morbidity and mortality) in septic neutropenic neonates must be weighed against the possible and reported side effects associated with such transfusions. Adverse reactions including graft-versus-host disease, CMV, HIV and hepatitis infection, fluid retention and pulmonary edema, blood group sensitization, and pulmonary insufficiency may all result from the use of granulocyte transfusions in a host who has evidence of developmental immaturity. All future studies must continue to evaluate these potential complications to balance and analyze the true benefits of survival with reported treatment results. Recently, a number of investigators including ourselves, have begun to examine the role of alternate adjuvant immunotherapy in enhancing neonatal host defense in the clinical setting of overwhelming bacterial sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of granulocyte transfusion in neonatal sepsis. 213 12

Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD.
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PMID:Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models. 622 Apr 91

Recipients of allogeneic bone marrow transplants are characterized by an immunodeficiency of varying intensity and duration. We have previously demonstrated the presence of in vivo activated suppressor T lymphocytes in immunodeficient patients with chronic graft-versus-host disease. To determine the basis of the immunodeficiency of transplant recipients early after transplantation, the lymphocytes of transplant recipients were analyzed phenotypically by E-rosette formation and staining with monoclonal antibodies (OKT-3, -6, and -8) and functionally by their blastogenic response to mitogens. Only 15% of transplant recipients' assays 0-3 months and 16% of assays 3-12 months following transplant were in the normal range. Transplant recipients during the first year after transplantation were characterized by an increased percentage (57%) of patients with a normal percentage of E-rosette-forming cells but reduced PHA responsiveness. In vitro coculture experiments demonstrated that their lack of PHA responsiveness was not due to the presence of in vivo activated suppressor cells or a decrease in mitogen-presenting cells. Staining with monoclonal antibodies revealed that the T lymphocytes from the majority of recipients at 0-3 months following transplantation contained a percentage of OKT8-positive cells greater than or equal to the percentage of OKT3-positive cells. This pattern (OKT8 greater than or equal to OKT3) was not found in the peripheral blood T lymphocytes of normal people but was found in 13 of 15 thymuses. Monoclonal staining with OKT6, a thymocyte-specific antibody, revealed positive staining of more than 10% of the peripheral blood leukocytes in the majority of recipients 0-3 months following transplantation, compared with only a few normals. We concluded that the circulating T lymphocytes of transplant recipients are phenotypically and functionally immature, and that their relative immaturity contributes to the transplant recipients' immunodeficiency.
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PMID:Immature T lymphocytes in the peripheral blood of bone marrow transplant recipients. 636 45

The number of umbilical cord cell transplants is increasing worldwide. The results are comparable to allogeneic bone marrow transplantation in a large variety of hematological diseases that are curable by bone marrow transplantation and, so far, the incidence of graft-versus-host disease has been limited. The advantages of using cord blood are related to the high number of hematopoietic progenitors present in the circulation at birth and to the relative immune immaturity of the newborn. A project is described to establish a European cord blood bank in order to obtain related or unrelated, matched or mismatched hematopoietic stem cells for transplantation to patients without a bone marrow donor.
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PMID:Blood banking for hematopoietic stem cell transplantation. 792 89

Interleukin-12 (IL-12) is a critical cytokine regulating natural killer (NK) and T-cell function. We hypothesized that the impaired ability of cord blood (CB) to produce normal adult levels of IL-12 in response to stimulation may contribute to the immaturity of CB immunity. Furthermore, exogenous IL-12 may compensate for the immaturity in CB cellular immunity and have the potential for immunotherapy post cord blood transplantation. We compared the expression and production of IL-12 from activated cord versus adult mononuclear cells (MNC), regulatory mechanisms associated with IL-12 expression in CB MNC, and the effects of IL-12 on induction of CB interferon (IFN)-gamma production, NK, and lymphokine-activated killer (LAK) cytotoxicity. Northern analysis and enzyme-linked immunosorbent assay were performed in lipopolysaccharide (LPS)-stimulated CB and adult peripheral blood (APB) MNC. IL-12 mRNA expression was induced within 6 hours with LPS (10 micrograms/ml) and reached peak levels at 12 hours in both CB and APB MNC. However, IL-12 mRNA expression and protein accumulation in CB MNC were 35.8% +/- 4.84% (12 hours, n = 11, P < .05), and 17.6% +/- 1.7% (24, 72, 96 hours, n = 9, P < .05) respectively, when compared with APB MNC. Nuclear run-on assays showed no differences between CB and APB MNC in both the basal levels of transcription and the degree of transcriptional activation. However, the half-life of IL-12 p40 mRNA was approximately threefold lower in activated CB MNC than in activated APB MNC (CB: 114 +/- 3.0 minutes v APB: 353 +/- 7.8 minutes, n = 3, P < .05). Exogenous IL-12 (10 U/mL) induced a significant increase of IFN-gamma from both CB and APB MNC (24 hours, 72 hours, P < .05, n = 3). The stimulated CB IFN-gamma level reached comparable levels produced by unstimulated APB. IL-12 treatment also significantly enhanced CB NK cytotoxicity against K562 and NB-100 cell lines to the comparable levels of APB (P < .05, n = 4). CB MNC was more responsive to IL-12 stimulation with respect to IFN-gamma production, NK, and LAK cytotoxicity when compared with APB. The present study suggests that IL-12 mRNA and protein expression is decreased in activated CB. This discrepancy in IL-12 production is secondary, at least in part, to the altered posttranscriptional regulation. The impaired, ability of CB MNC to produce IL-12 in response to stimulation may contribute to the decrease in IFN-gamma production and NK cytotoxicity. However, IL-12 enhanced IFN-gamma and NK activity in CB MNC up to the comparable levels of APB MNC. These findings suggest that reduced expression and production of IL-12 from activated CB may contribute to the immaturity in CB cellular immunity and contribute, in part, to decreased graft-versus-host disease following CB stem cell transplantation.
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PMID:Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon-gamma, natural killer, and lymphokine-activated killer activity by IL-12 in cord blood mononuclear cells. 870 53

Based on our experience in the field of fetal liver transplantation (FLT) that we have developed since 1976, we initiated, in 1988, in utero FLT into human fetuses, taking advantage of the immunologic tolerance in young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization, with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed. Three children are more than 4 years old, and they are alive and well, with evidence of engraftment, reconstitution of immunity, and partial correction of beta-thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to immune immaturity of the host, (b) lack of graft-versus-host disease (GVHD) due to immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factors.
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PMID:In utero transplantation of fetal liver stem cells into human fetuses. 872

Since 1976, we have performed more than 240 fetal tissue transplants (FLTs) to treat 63 patients with severe immunodeficiency disease (IDD), with inborn errors of metabolism (IEM), or with severe aplastic anemia. In both IDD and IEM, FLT into postnatal recipients has demonstrated beneficial effects (67%) of the patients were either cured or improved significantly). In 1988, we developed in utero FLT into human fetuses, taking advantage of the immunological tolerance of young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed: 3 children are now more than 4 years old, and are alive and well with evidence of engraftment, reconstitution of immunity, and partial correction of beta zero thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to the immune immaturity of the host, (b) lack of graft-versus-host disease due to the immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) an optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factors.
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PMID:Treatment of human fetuses and induction of immunological tolerance in humans by in utero transplantation of stem cells into fetal recipients. 887 6

Hematopoietic stem cell (HSC) transplantation in children and adults with congenital lymphohematopoietic disorders is limited by donor availability, graft failure, graft-versus-host disease (GVHD) and delayed immunological reconstitution. These problems may be circumvented by transplanting the patient before birth. Prenatal cellular therapy for the treatment of congenital diseases has tremendous theoretical appeal. Potential advantages of prenatal transplantation include: A) fetal immunologic immaturity and the potential for induction of donor-specific tolerance; B) available space in the developing bone marrow for engraftment of donor cells; C) the sterile, protective, fetal environment which provides isolation from environmental pathogens, and D) prevention of clinical manifestations of the disease. Normal hematopoietic and immunologic development during ontogeny creates a "window of opportunity" during which events favor the engraftment of transplanted allogeneic (and xenogeneic) HSC and their proliferation. This is a period in which the fetus is immunologically naive and thus incapable of rejecting the foreign HSC, and the expanding bone marrow spaces allow homing and engraftment of HSC without the need for myeloablation. Experiments in sheep have established the optimal age of the recipient, route of donor cell administration, sources of HSC, and other parameters necessary for the successful engraftment and long-term expression of donor HSC. In preclinical studies, transplantation of CD34-enriched or highly purified populations of human adult bone marrow cells in utero resulted in the long-term engraftment and expression of donor HSC without graft failure and GVHD. The strategies developed in allogeneic and xenogeneic fetal sheep models were used to successfully treat human fetuses with X-linked recessive severe combined immunodeficiency.
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PMID:Transplantation of hematopoietic stem cells in utero. 936 28

Hematopoietic progenitor cells are present in umbilical cord blood; placental blood (PB) previously considered as waste product now constitutes an alternative source of hematopoietic stem cells for bone marrow reconstitution. This has promoted the establishment of cord blood banks for use in unrelated transplants. The banking of PB offers many advantages: the donors do not require anesthesia, stored PB can be a valuable source of stem cells for patients from ethnic minorities underrepresented in volunteer registers, and stored PB can be made available much faster than bone marrow from unrelated donors. Preliminary clinical experience suggests that, due to the immunological immaturity of PB cells, graft versus host disease might be lower than when using bone marrow from adult donors and HLA restrictions might be less stringent. If the number of nucleated cells in PB often appears low for patients weighing more than 40 kg, clinical data suggest that the number of stem cells may be sufficient for adult transplantation. The number of cord blood banks throughout the world is increasing rapidly. In the USA and Europe, more than 10,500 PB units are stored and available for transplantation. In the next 5 years, a total of 50,000 PB will be reached which may be sufficient to provide for the majority of candidates for unrelated BM transplantation. The practices of umbilical cord blood collection, mother selection, infectious disease screening, cell manipulation and storage must be standardized. Some accreditation process should be mandatory for assessing operating procedures and the quality assurance programs of the banks, and for allowing the international exchange of placental blood between transplant centers.
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PMID:[Cord blood banks--unrelated transplants]. 957 80


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