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)

Calcium and sodium permeability of erythrocytes from patients with untransfused alpha- or beta- thalassemia major has been studied and compared to mature erythrocytes or control cells with comparable reticulocytosis. Isotopic Na(+) influx was increased a mean fourfold greater than normals and threefold greater than reticulocyte rich control. Passive net leak of Na(+) into thalassemic cells incubated with ouabain was also increased corresponding to their greater (22)Na(+) influx. Erythrocyte Na(+) and K(+) concentrations and cell water content per unit volume of cells were normal. Quantitation of active cation pumps in the cell membrane by the technique of [(3)H]ouabain binding showed a 2.6- to 9.9-fold increase above normal. Inward Ca(2+) movement was studied in cells with absent Ca(2+) pumping produced by depletion of either ATP or Mg(2+)-ions. Calcium uptake by ATP depleted thalassemic cells was increased 12-fold above normals and 3.6-fold above reticulocyte-rich controls. The Ca(2+) uptake by Mg(2+)-depleted thalassemic cells was also increased above normal confirming that erythrocyte Ca(2+) permeability is increased in this disease. Osmotic fragility measurements show that the surface area to volume ratio of thalassemic erythrocytes was increased by 15 to 25% above mature erythrocytes. The increased passive cation permeability of thalassemic erythrocytes cannot be explained by either reticulocytosis or an increased surface area to volume ratio of these cells. Moreover, erythrocyte Na(+) and Ca(2+) influxes in congenital dyserythropoietic anemia (CDA type 2) were increased 2- and 14-fold, respectively, above normal. The increased cation fluxes and cation pump numbers in thalassemic and congenital dyserythropoietic anemia erythrocytes are consistent with the hypothesis of membrane immaturity arising from rapid marrow transit times, a concept previously advanced to explain the persistence of i-antigen on these cells.
 ...
PMID:Increased erythrocyte cation permeability in thalassemia and conditions of marrow stress. 720 77

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