Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following 18 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The four fetuses that we treated were 28, 26, 17 and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the two other had thalassemia major. Donor cells were obtained from 7- to 12-week-old fetuses, with conditions approved by the National Committee for Bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of three patients and injected intraperitoneally into the other one, under ultrasonic visualization. The first patient, bone in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% then 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989; donor cell engraftment has been proven (Y chromosome in this female patient) and immunological reconstitution is in progress, allowing a normal life at home. The third patient has also evidence of donor cell take (Y chromosome in a female patient) and a partial effect on thalassemia has been documented (donor haemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rationale and results of in utero transplants of stem cells in humans. 135 82

Following 15 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The three fetuses that we treated were 28, 26, and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the third one had thalassemia major. Donor cells were obtained from 7- to 10-week-old fetuses, with conditions approved by the National Committee for Bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% than 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989 and it is too early for a thorough evaluation of the immunological effects of the transplant, although donor cell engraftment has been proven (Y chromosome in this female patient). The third patient has also evidence of donor cell take (Y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In utero transplantation of fetal liver stem cells in humans. 168 May 6

Based on the experience acquired in post-natal liver transplantation since 1974, we recently initiated pre-natal, in utero stem cell transplantation from the human fetal liver. The first two fetuses that we treated had immunodeficiencies, the third one had thalassemia major. Donors and recipients were not matched. The fetal cells were infused in the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has both engraftment of donor cells and reconstitution of cell-mediated immunity. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and he lives normally at home. The second child, born in 1989, has not yet developed a significant reconstitution of immunity although donor cell engraftment has been proven (Y chromosome in this female patient). The third patient has also evidence of donor cell take (Y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all 3 cases, no side-effect of any kind developed in the mother nor in the fetus. Several advantages appear to be associated with in utero FLT: increased probability of graft take, ideal isolation of patient (in the uterus), optimal environment for fetal cell development (in the fetal host).
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PMID:New developments in stem cell transplantation with special reference to the first in utero transplants in humans. 185 99

We report the development of a rapid nonradioactive technique for the genetic prediction of human disease and its diagnostic application to hemophilia A. This method is based on enzymatic amplification of short segments of human genes associated with inherited disorders. A novel feature of the procedure is the use of a heat-stable DNA polymerase, which allows the repeated rounds of DNA synthesis to proceed at 63 degrees C. The high sequence specificity of the amplification reaction at this elevated temperature permits restriction-site polymorphisms, contained in the amplified samples, to be analyzed by visual inspection of their digestion products on polyacrylamide gels. By means of this method, we have performed carrier detection and prenatal diagnosis of hemophilia in two families with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes BclI and XbaI. Predictions can be made directly from chorionic villi, without previous DNA extraction, and fetal sex can be determined by amplification of sequences specific for the Y chromosome. Specific amplification of genomic sequences with heat-stable DNA polymerase is applicable to the diagnosis of a wide variety of inherited disorders. These include diseases diagnosed by restriction-site variation, such as Duchenne's muscular dystrophy and sickle cell anemia, those due to a collection of known mutations, such as beta-thalassemia, and those due to gene deletion, such as alpha-thalassemia.
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PMID:An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. Application to hemophilia A. 365 65

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.
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PMID:Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies. 861 Apr 14

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.
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PMID:Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/lepore haemoglobinopathy. 1009 Nov 84

An extra Y chromosome(s) is occasionally found in patients with various hematologic neoplasias; however, an association with hereditary blood diseases is unknown. In a child with beta-thalassemia who received a transplant with sex-mismatched umbilical cord blood and neonatal blood, fluorescent in situ hybridization (FISH) with probes to X and Y chromosomes revealed an extra Y signal in 19.3% of the hepatocytes and in 38.9% of the pretransplant peripheral blood cells, yielding YY/Y ratios of 0.24 and 0.64, respectively. In granulocyte colony-stimulating factor-mobilized autologous peripheral blood stem cells, the FISH ratio of interphase XYY cells to XY cells was 1.64, and there were 3.4 times more G-banded XYY metaphases than normal metaphases. Both FISH and polymerase chain reaction persistently demonstrated posttransplant mixed chimerism. There was a greater proportion of residual autologous XYY cells than XY cells with a mean posttransplant YY/Y ratio of 1.56 (n = 13) (1 SD = 0.33; range, 1.10 to 2.17). In vitro clonogenic assays yielded a normal number of colony-forming units but no growth in cultures without growth factor supplement. This study suggests that hematopoietic stem cells with an extra Y chromosome may upregulate cell growth in response to cytokine stimulation. A posttransplant preponderance of XYY cells might be attributable to an extra Y chromosome in hematopoietic stem cells withstanding the myeloablative conditioning regimen.
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PMID:Up-regulation of cell growth associated with an extra Y chromosome in a child with beta-thalassemia major having undergone hematopoietic stem cell transplant. 1077 26

OBJECTIVE: To investigate the feasibility of multiple loci detection in single cell by primer extension preamplification (PEP) followed by nest PCR. METHODS: Using PEP, the whole genomic DNA in single lymphocyte or single blastomere was amplified. In addition, CD17, nt-28 and linked ATTTT repeat for beta-thalassemia, F508 and linked GATT repeat for cystic fibrosis, DMD exon 17 and 48 for Duchenne muscular dystrophy, short tandem repeats of D18S51, D21S11 and D21S1411, and sex-determination gene SRY of the Y chromosome were all detected using nest-PCR from a small aliquot of the PEP reaction. RESULTS: The rate of successful single lymphocyte amplification was 89.5%(false positive 0.48%false negative 2.5%). The rate of successful single blastomere amplification was 85.56%(false positive 3%). CONCLUSION: The PEP technique followed by nest PCR analysis of single cell is very useful for simultaneous detection of multiple gene loci. It may be applicable for preimplantation genetic diagnosis.
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PMID:[Detection of multiple loci in single cell by primer extension preamplification and nest PCR] 1259 99

The frequency, distribution pattern and localisation of gamma radiation-induced break points on the chromosomes of patients with various inherited metabolic disorders were studied to detect: (i) whether the break point distribution following irradiation is random and proportional to the length or the DNA content of the chromosome, or non-proportionally distributed on their length and at times clustering to form hot spots on certain region of the chromosomes; and (ii) to find whether there exists a syndrome-related chromosome-specific pattern of radiation-induced break points. Lymphocyte cultures from patients of haemophilia, ichthyosis, Duchenne muscular dystrophy, retinitis pigmentosa and alpha-thalassemia, whose defective gene loci were located by DNA probe method, were subjected to 3Gy of gamma radiation at G(0). The chromosomal break point analysis was carried out on all the 23 types of chromosomes (excluding Y chromosome) using G banding and FISH painting. The exact location of the break points on G-banded chromosomes was identified using a semi-automated microscope densitometer system (Leitz MPV2). In normal individuals in all the chromosomes except the chromosome 1, a random distribution of break points proportional to their length based on their DNA content was observed. However, in all the syndromes studied a mixture of hypersensitive chromosomes with a non-random distribution pattern of chromosomal break points invariably clustering to form hot spots, and chromosomes with random distribution of break points proportional to their length were observed. The hypersensitive chromosomes and their hot spots were syndrome-specific.
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PMID:Syndrome-related chromosome-specific radiation-induced break points of various inherited human metabolic disorders. 1283 62