Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five patients with classic hemophilia were found to have primary pulmonary hypertension, a disorder not previously recognized in this population. All patients had had their coagulation disorder treated for 10 years or more with self-administered lyophilized concentrates of factor VIII, and all had antibodies to human immunodeficiency virus (HIV). Primary pulmonary hypertension was confirmed by histologic means at autopsy in one patient and by lung biopsy findings in another. In the other three patients, the findings are in agreement with this diagnosis. No patient had underlying cardiac or pulmonary disease, or clinical or pathologic evidence of collagen-vascular disease, vasculitis, parasitic disorders, hemoglobinopathy, or exposure to anorexigenic agents. Whether the primary pulmonary hypertension was related to treatment with lyophilized factor VIII, or to the presence of antibodies to HIV, or both, is unknown.
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PMID:Primary pulmonary hypertension in patients with classic hemophilia. 280 26

Anemia is responsible for an estimated 20% of maternal deaths in West Africa and contributes to still more deaths through obstetric hemorrhage. Anemia during pregnancy has been linked to iron and folate dietary deficiencies, the secondary effects of malaria and hookworm infestations, infections such as human immunodeficiency virus, and hemoglobinopathies. Parasitic infestations interfere with the normal increase (given a balanced diet) in iron absorption during pregnancy. An understanding of locally salient etiologic factors should form the basis of public health programs aimed at addressing anemia during pregnancy. There is a need for basic prevalence statistics, especially from West Africa's rural areas. Finally, reliable laboratory parameters that can be used in the assessment of iron and folate status and the degree of anemia attributable to malaria must be established. Although there is emerging evidence that serum transferrin receptor concentration is not affected by chronic disease or the physiological changes of pregnancy, further studies are needed to validate this measure.
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PMID:The aetiology of anaemia in pregnancy in West Africa. 913 12

Sickle cell disease (SCD) is characterized by significant morbidity and early mortality. Children with this hemoglobinopathy exhibit many of the manifestations associated with immunodeficiency disorders. Serum was obtained from 56 healthy SCD subjects and 45 normal healthy controls. Type 2 cytokines interleukin (IL)-4, IL-6, and IL-10 serum levels were measured. Concentrations were determined by reference to a standard curve, and results were expressed in pg/mL. Results revealed significant levels of IL-4 in 6 (13%) of 45 SCD patients compared with 1 (2%) of 45 controls. Increased levels of IL-6 were present in 35 (78%) of 45 SCD patients and 12 (41%) of 29 controls. Elevated levels of IL-10 were detectable in 13 (41%) of 42 SCD patients and 1 (4%) of 25 controls. High circulating levels of type 2 cytokines may suppress both humoral and cell-mediated immune functions in SCD, with resultant increased morbidity.
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PMID:Type 2 cytokine serum levels in healthy sickle cell disease patients. 937 80

In utero hematopoietic stem cell transplantation is a promising approach for the treatment of a variety of congenital hematologic diseases. Although the approach has been successful for immunodeficiency syndromes, attempts thus far to treat the hemoglobinopathies have failed. In most of these cases the late gestational age at transplantation, source of donor cells, or procedure-related complications, provide an explanation for failure. Nevertheless the biology of thalassemia, in the context of prenatal transplantation, requires examination. In contrast to postnatal bone marrow transplant regimens, engraftment after in utero transplantation requires donor cells to effectively complete for developing receptive sites in the recipient hematopoietic microenvironment. Effective prenatal treatment of thalassemia will depend on the ability of normal cells to engraft and complete in the thalassemic microenvironment. Clinical observations after bone marrow transplantation of amelioration of anemia in beta-thalassemia by relatively low degrees of mixed chimerism, and the apparent selective advantage observed for donor erythropoiesis, suggest prenatal transplantation could succeed. Prenatal strategies involving multiple transplants, donor-specific tolerance induction, and postnatal same-donor transplants should be considered.
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PMID:In utero transplantation for thalassemia. 966 52

Successful prenatal treatment of severe immunodeficiencies by allogeneic hematopoietic stem cell transplantation in utero has been reported. Though other diseases like hemoglobinopathies or storage diseases are potentially amenable to this novel therapeutic approach, no success has yet been achieved in recipients without severe immunodeficiency. Graft rejection by the developing fetus and/or lack of selective, competitive advantage of donor versus host stem cells preventing stable engraftment seem to be the major obstacles. Several strategies to overcome these hurdles are being explored in preclinical settings, including timing and repeated dosing of stem cell administration to the fetus, ex vivo modification of the transplant, using different fetal compartments as targets for early stem cell transfer, or inducing microchimerism for postnatal transplantation from the same donor. In addition, the exact definition of the basic concept of early fetal immunologic naivete and the understanding of the molecular basics of migration and homing in fetal hematopoiesis system seem mandatory for a successful approach. Gene therapy using ex vivo transduced autologous cord blood cells or direct gene targeting in utero are other potential means to correct hematopoietic and immunologic single gene disorders in utero, though this approach is still away from the stage of clinical trials.
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PMID:In utero hematopoietic stem cell transfer: current status and future strategies. 1042 33

In utero stem cell transplantation represents a new and still experimental therapeutic strategy for diseases related to the hematopoietic system, i.e. hemoglobinopathies, immunodeficiency diseases and metabolic disorders. To date, a total of 21 cases of transplantations using stem cells either of fetal liver or adult bone marrow origin have been reported in the literature. Success has been limited--with the exception of one case of beta-thalassemia--to four cases with immunodeficiency diseases. In this review the broad therapeutic implications as well as potentials and limitations of this technique are summarized. Furthermore, ethical considerations based on the use of fetal cells are pointed out and a prospective view concerning experimental and clinical future perspectives including the possibility for gene therapy is presented.
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PMID:Stem cell therapy in utero. 1112 24

Several inherited diseases can now be treated using postnatal or prenatal, in utero, transplantation of stem cells from the human fetal liver. Twenty-four patients with severe immunodeficiency diseases have been treated in infancy and three at the fetal stage, in our institution. We have also treated similarly 34 patients with inborn errors of metabolism or hemoglobinopathies. A total of 64% of all patients are alive with either full cure of their initial disease or at least significant benefit from the treatment. Immunological reconstitution can develop despite full mismatch between the stem cell donor and the recipient patient. Tolerance is acquired both towards donor and host antigens. Gene therapy is starting its development in some infants with an immunodeficiency related to a known gene defect and, in the future, it may be used in fetuses, immediately after the prenatal diagnosis of the gene abnormality.
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PMID:Perinatal fetal-cell and gene therapy. 1113 10

Hematologic diseases potentially benefiting from gene-based therapies involving hematopoietic stem cells (HSCs) include hereditary hemoglobinopathies, immunodeficiency syndromes, and congenital bleeding disorders such as hemophilia A, as well as acquired diseases like AIDS. Successful treatment of these blood diseases with gene-modified HSCs requires high efficiency gene delivery to the target cell population and persistence of transgene expression following differentiation. We review flow cytometric procedures that permit simultaneous, noninvasive measurements of transgene expression and phenotypic discrimination of hematopoietic cell subsets. Central to this approach has been the recent development of a spectrum of blue, cyan, and yellowish-green fluorescent reporters based on the jellyfish Aequorea victoria green fluorescent protein and the discovery of a red fluorescent protein in DISCOSOMA: coral. This methodology should facilitate the optimization of oncoretroviral and lentiviral vectorology and HSC transduction protocols for the ultimate purpose of HSC-directed gene therapy.
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PMID:"Rainbow" reporters for multispectral marking and lineage analysis of hematopoietic stem cells. 1123 66

Monthly hemochrome parameters were obtained during the first 2 years of age in 22 children with perinatal human immunodeficiency virus type-1 (HIV-1) infection and in 58 exposed seroreverted children. Timing and predictive value of hemochrome modifications were investigated. Exclusion criteria were hemoglobinopathies and zidovudine (AZT) treatment in pregnancy. When AZT treatment was undertaken children were eliminated from the study. From the second month of life red blood cell (RBC) counts, hemoglobin (Hb) concentrations, and hematocrit values were significantly lower in infected than in uninfected children. RBC counts progressively diverged in infected and uninfected children, and mean values in the former group never reached 4.10(12)/L. No difference was observed in Hb content ratios and RBC size parameters. At 2 months RBC counts, Hb concentrations, and hematocrit values below reference values were associated with a 15.8 (95% confidence limits [CL]: 5.5-48.8) relative risk of being infected. In infected infants aged 5 months a decrease in these parameters was associated with an 11.2 (95% CL: 1.6-77.8) relative risk of developing eventual severe clinical outcome. Low RBC counts, Hb concentrations, and hematocrit values may be included among predictive criteria in infants of HIV-1 infected mothers.
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PMID:Hemochrome parameters during the first two years of life in children with perinatal HIV-1 infection. 1136 57

Although most of the diagnostic applications of flow cytometry bring forth examples of leukocyte immunophenotyping for immunodeficiency diseases and leukemia-lymphoma diagnosis, the same technology has improved medical assessment of diseases affecting the red cell and erythropoiesis. Flow cytometric methods were first applied to laboratory hematology with the improvement in reticulocyte counting and the creation of the immature reticulocyte fraction for better anemia evaluation and therapeutic monitoring. A more recent improvement attributable to flow cytometry is accurate detection of fetal red cells in the evaluation of FMH hemorrhage. The same method used in the detection of fetal RBCs based on HbF content measurement using monoclonal antibodies also offers the potential for enumeration of F cells, which promises to have use in therapeutic monitoring of patients with sickle cell disease and the evaluation of other hemoglobinopathies and myelodysplasia. Other clinical uses of flow cytometric RBC analysis include nonisotopic red cell survival studies, sensitive blood group typing, sensitive detection of immune-mediated hemolytic diseases, and evaluation of parasitic diseases whose life cycle involves intracellular RBC infestation. This article summarizes red cell flow cytometry, particularly as it impacts the areas of immunohematology and laboratory hematology, and points to areas of potential future contribution of this technology to diagnostic medicine.
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PMID:Diagnostic utility of red cell flow cytometric analysis. 1177 Feb 90


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