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

Human umbilical cord blood has proven to be a feasible alternative source of hematopoietic stem cells for pediatric and some adult patients with major hematologic disorders. This has promoted the establishment of cord blood banks for use in unrelated transplants worldwide. The banking of umbilical cord blood offers many advantages: absence of donor risk, absence of donor attrition, immediate availability, and the ability to expand available donor pools in targeted ethnic and racial minorities currently underrepresented in all bone marrow registries. Preliminary clinical experience suggests that, due to the immunological immaturity of cord blood cells, graft versus host disease might be lower than when using bone marrow from adult donors and HLA restrictions might be less stringent. Techniques to improve the efficacy of blood banks are currently under investigation. Closed cord blood collection methods have proven to be superior to open in reducing the risk of microbial contamination. Efficient banking requires volume reduction of cord blood units without significant loss of progenitor cells, in order to decrease storage space and cost, and this may be achieved by using the separation techniques. Cryopreservation and thawing techniques have been established and do not seem to affect the viability and progenitor cell recovery or the feasibility of CD34(+) selection and ex vivo expansion. Nevertheless, many scientific, ethical, and social questions have arisen in connection with cord blood banking that need to be addressed.
 ...
PMID:Human umbilical cord blood banking and transplantation: a state of the art. 1076 5

Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs). Ten patients who underwent CB transplantation for high-risk hematologic disorders were compared to a reference group of 19 age- and GVHD-matched patients who underwent transplantation with non-T cell-depleted bone marrow from an HLA-identical sibling donor. TREC values correlated with the relative number of naive T cells and with TCR repertoire polyclonality. During the first year after transplantation, TCR repertoires were highly abnormal and TREC values low in both groups. Notably, 2 years after transplantation onward TREC values as well as TCR diversity were higher in CB recipients than in recipients of bone marrow transplants. These data indicate an efficient thymic regeneration pathway from CB lymphoid progenitors despite the low number of cells infused compared to bone marrow, arguing for a complete clinical immune recovery after CB transplantation.
 ...
PMID:A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation. 1183 May

Insulin-dependent neonatal diabetes (ND) mellitus is uncommon with a frequency of 1/500,000 neonates in Europe. ND is characterised by hyperglycaemia, very low or undetectable insulin levels associated with intrauterine growth retardation and malformations. HLA haplotypes of juvenile diabetes or autoimmunity are not present in ND patients. Sporadic and familial forms are observed. ND could be persistent (PND) or transient (TND). Diabetes relapses occur in approximately 40% of TND patients. Hypothesis for ND aetiology such as pancreatic or beta pancreatic islets of Langerhans immaturity or abnormalities of pancreas organogenesis are postulated. Different genetic basis underlie transient or permanent forms though their clinical features do not allow to distinguish them. TND may in about 20-30% of the cases be associated with chromosome 6 paternal uniparental disomy. A candidate locus for an imprinted gene is mapped to 6q24. The permanent forms are less understood. Homozygous mutations of the IPF1/PDX1 (MODY4) and of the Glucokinase (GK, MODY2) genes have been reported. The association of a ND with a macroglossia should be a strong indicator for genetic testing. The genetic findings of a paternal disomy uniparental allows the prediction of a transient rather than a permanent form. Mutation in the Glucokinase gene should be sought in an infant with ND whose first degree relatives have glucose intolerance.
 ...
PMID:[Insulin-dependent neonatal and infant diabetes: genetics and physiopathology]. 1208 68

Haematopoietic stem cell transplantation is indicated in several haematologic and genetic diseases, the most notable being aplastic anemia and leukemias. Bone marrow has been the traditional source of these cells. Human umbilical cord blood (UCB) has recently become an alternative source of haematopoietic stem cells for transplants. The advantages of cord blood include noninvasive collection without risk to mother and neonate, low risk of viral infection, and immunologic immaturity of cord cells. Single umbilical cord blood donation is usually sufficient for transplantation to adult recipients. Additionally, banking of HLA-typed UCB appears valuable in patients lacking a family donor. This study has focused on basic "perinatological" parameters of umbilical cord blood: average volume of single donation UCB and initial storage conditions before isolation of haematopoietic stem cells. Additionally, the mean content of CD34+ haematopoietic stem cells in leukocyte, lymphocyte and mononuclear cell fractions was established. Correlations between levels of so-called pro-inflammatory cytokines (present in cord blood serum) and number, viability and clonogenicity of cord blood mononuclear cells were checked. UCB samples were obtained by "open" collection during vaginal deliveries and cesarean sections. The collected blood was stored in solutions of anticoagulants (ACD, CPDA-1, heparin) and culture media (PBS, Iscove medium, RPMI), during several time intervals (0-1 h, 1-6 h, 6-12 h, 12-24 h) and at two temperatures (+4 degrees C, ambient). UCB volumes, as well as MNC counts, correlated with delivery type, placental weight, neonatal body weight and duration of pregnancy. The concentration, viability and clonogenicity of MNCs were assessed after collection and storage. The subpopulation of CD34+ haematopoietic stem cells was isolated from MNCs using monoclonal antibodies and magnetic-based separation. The number, viability and clonogenicity of CD34+ cells were evaluated. Subsequently in some samples, the concentration of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha), number of mononuclear cells and in vitro clonogenicity of myeloid progenitors (CFU-GM) were determined. It was found that the collected blood volume depended on neonatal body weight (Fig. 1). Umbilical blood could be stored either at ambient temperature (Fig. 4) or +4 degrees C (recommended because of reduced risk of infection) for up to 24 hours in RPMI solution (Fig. 5) with heparin (Fig. 2, 3). CD34+ cell count correlated with mononuclear cell count only (Fig. 6). A negative correlation between the number of mononuclear cells and concentration of TNF-alpha was revealed (Fig. 7), as well as between the number of detectable CFU-GM and concentration of IL-1 beta (Fig. 8). In conclusion, UCB collection and short-term storage is a safe and simple method for graftable haematopoietic stem cell recovery. Save for IL-1 beta and TNF-alpha, cytokine levels did not correlate with the studied parameters of umbilical cord blood.
 ...
PMID:[Improved method for delivery room collection and storage of human cord blood cells for grafting]. 1251 5

Infant immunization is the most cost-effective strategy to prevent infectious diseases in childhood, but is limited by immaturity of the immune system. To define strategies to improve vaccine immunogenicity in early life, the role of genetic and environmental factors in the control of vaccine responses in infant twins was studied. Immune responses to BCG, polio, hepatitis B, diphtheria, pertussis and tetanus vaccines were measured at 5 months of age in 207 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variation in responses. High heritability was observed for antibody (Ab) responses to hepatitis B (77%), oral polio (60%), tetanus (44%) and diphtheria (49%) vaccines. Significant heritability was also observed for interferon-gamma and interleukin-13 responses to tetanus, pertussis and some BCG vaccine antigens (39-65%). Non-HLA genes played a dominant role in responses to Ab-inducing vaccines, whereas responses to BCG were predominantly controlled by genes within the HLA class II locus. Genetic factors, particularly non-HLA genes, significantly modulate immune responses to infant vaccination. The identification of the specific genes involved will provide new targets for the development of vaccines and adjuvants for young infants that work independently of HLA.
 ...
PMID:Genetic regulation of immune responses to vaccines in early life. 1473 96

The therapeutic field of in utero transplantation of stem cells, into human fetuses, has developed since 1988 with the hope of improved probability of engraftment and tolerance, due to immune immaturity of the host. Fifteen years later, it is possible to evaluate the results that we and others have obtained in the treatment of several fetal diseases. Seven fetal patients have been treated in Lyon: In 2 cases, pregnancy termination was induced by the in utero injection; in the 5 other cases, engraftment was obtained and repeatedly documented with presence of donor HLA antigens and/or Y chromosome in recipients. In the 2 patients with combined immunodeficiency disease, a sustained reconstitution of immunity was obtained as a result of the transplant but other complications occurred thereafter. In patients with thalassemia major, Niemann-Pick disease or hemophilia, a very partial and very transitory benefit was only obtained. Approximately 33 other patients with immunodeficiencies, hemoglobinopathies or inborn errors of metabolism have been treated worldwide, over the last 13 years, with a comparable method, using parental or fetal stem cells transplanted in utero. Successful treatment has usually been recorded in immunodeficiencies, and insufficient results have been obtained in the other cases. This form of treatment can therefore be recommended after prenatal diagnosis of combined immunodeficiency but additional research is required to improve the degree of engraftment, the lack of resistance of the host and the 'space' available for hematopoiesis in the other conditions.
 ...
PMID:Reappraisal of in utero stem cell transplantation based on long-term results. 1519 88

The first cord blood (CB) transplant was performed in 1988 in a patient with Fanconi anemia. The donor was his HLA-identical sister who was known by pre-natal diagnosis to be HLA identical and not affected by the Fanconi mutation. The CB was collected and cryopreserved at birth. The transplant was successful without GvHD and the patient is currently alive and free of disease more than 15 years after transplant, with full hematologic and immunologic donor reconstitution. At the time of the first transplant, little was known about the biologic properties of CB cells and it was thanks to the pioneering work of H. E. Broxmeyer and E. A. Boyse, who studied the progenitor cell content of CB, and of A. D. Auerbach, who realized the pre-natal diagnosis of Fanconi anemia, that this transplant was possible. Since this first transplant, many questions have been answered but others are still open for further research. For example: would a single CB unit contain enough stem cells to permanently engraft children and adults? Would maternal cell contamination in fetal blood engraft and give severe GvHD? What are the immunologic properties of CB cells? How does it interfere with GvHD, GvL and immune reconstitution? Is the immune immaturity of CB lymphocytes able to overcome the HLA barrier and authorize HLA-mismatched transplants? Is it possible to establish CB banks for unrelated and related transplants? What would be the criteria for collection, quality control and cryopreservation?
 ...
PMID:History of the clinical use of umbilical cord blood hematopoietic cells. 1608 48

Vertical exposure to HIV occurs at a time when functional capacity of the infant's immune system is attenuated through immaturity. Immune response capability is rooted in host genetic makeup, and the broad and fine specificity of innate and adaptive immune responses, respectively, shape the outcomes of HIV encounter in some instances and imprint viral changes through selective immune pressure in others. Findings from recent studies have profound implications for understanding immune pathogenesis of pediatric HIV infection and, in particular, highlight the importance of host genetics of both mother and child in determining whether an exposed child acquires HIV infection or not and, if infected, the rate of disease progression. This review focuses on the key host molecules, the CC chemokine CCL3 and HLA, which have taken center stage in these new developments.
 ...
PMID:Immune pathogenesis of pediatric HIV-1 infection. 1652 54

Dendritic cells (DCs) have been characterized as having an immature phenotype in infants when compared with adults; but it is unclear whether the phenotype or function of these populations changes during human intrauterine development. Three-colour flow cytometry was used to phenotype fetal/neonatal circulating DCs during the second half (>20-wk gestation) of pregnancy, (n = 34) and adults (n = 9). DCs were identified from peripheral blood mononuclear cells (PBMCs) or cord blood mononuclear cells (CBMCs) as staining brightly for HLA-DR but negative for T cell, B cell, monocyte, and NK cell lineage markers. The surface molecule of interest was detected in a third colour. During gestation CD34, a marker of immaturity was significantly higher, and CD4, a differentiation marker, was significantly lower than adult levels. The percentage of CD11c+ cells did not differ significantly at any age, although a trend to reduced intensity of expression at earlier stages of gestation was observed. Significantly fewer DCs expressed the IgG receptors CD32 and CD64 at all gestations. The percentage of HLA-DR+/lin- cells expressing CD40 was lowest at 20-23 wks and was always significantly lower on DCs from cord blood vs. adult blood. Similarly, the percentage of CD86+ and CD54+ DCs was significantly lower than adults throughout gestation. Thus, immaturity of cord blood DCs is likely to arise as a consequence of decreased ability to take up antigen (at least via IgG-mediated mechanisms) and reduced provision of co-stimulation.
 ...
PMID:Phenotypic analysis of circulating dendritic cells during the second half of human gestation. 1879 98

Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation.
 ...
PMID:Cord blood-derived hematopoietic stem/progenitor cells: current challenges in engraftment, infection, and ex vivo expansion. 2160 39


<< Previous 1 2 3 Next >>