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)

The regulation of mRNA decay is a major control point in gene expression. The stability of a particular mRNA is controlled by specific interactions between its structural elements and RNA-binding proteins that can be general or mRNA-specific. Regulated mRNA stability is achieved through fluctuations in half-lives in response to developmental or environmental stimuli like nutrient levels, cytokines, hormones and temperature shifts as well as environmental stresses like hypoxia, hypocalcemia, viral infection, and tissue injury. Furthermore, in specific disorders like some forms of neoplasia, thalassemia and Alzheimer's disease, deregulated mRNA stability can lead to the aberrant accumulation of mRNAs and the proteins they encode. This review presents a discussion of some recently identified examples of regulated and deregulated mRNA stability in order to illustrate the diversity of genes regulated by alterations in the degradation rates of their mRNAs.
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PMID:Regulation of mRNA stability in mammalian cells. 1125 3

A 40-year-old Xhosa male presented with progressive upper lumbar back pain and weakness At examination he was emaciated and had enlarged lymph nodes in the groin and axilla. Both lower limbs were severely atrophic and weak. Sensation to touch and pain was decreased below L3 bilaterally. MR of the spine showed a discrete, contrast-enhancing epidural mass. A T10-T12 laminectomy revealed an soft, vascular extradural tumor dorsal to the cord. The mass was loosely applied to the dura and easy to remove. The operative specimen consisted of a sausage-shaped (3.5 x 2.0 x 1.2 cm), thinly-encapsulated mass of reddish-brown tissue. The cut surface had a mottled, vaguely nodular, yellowish-brown appearance. Microscopic examination revealed sheets of hematopoeitic elements, including myeloid, red cell and megakaryocytic lines, the latter showing Factor 8-related positivity. The final diagnosis was extramedullary hematopoiesis (EMH). A bone marrow biopsy performed as a result of the diagnosis showed a myeloproliferative disease and polycythemia vera. EMH in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological disorders. Since 1956 there have been more than 50 reported cases, most of which occurred in association with thalassaemia. In spinal cord compression secondary to EMH, the lesions are commonly localized to the mid-lower thoracic region.
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PMID:October 2001: 40-year-old Xhosa male with back pain and leg weakness. 1195 81

Ganglioneuromas are rare benign tumors of neural crest origin, arising from ganglia of the sympathetic nervous system and adrenal medulla. These masses are usually detected during the first 2 decades of life and are generally discovered incidentally. We present a 5-year-old boy with sickle beta-thalassemia whose hypertension is caused by a perihilar ganglioneuroma encasing the right renal artery and distorting the right renal vein. The tumor was resected and the child's blood pressure subsequently normalized.
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PMID:An unusual etiology of hypertension in a 5-year-old boy. 1217 67

Iron is an essential mineral for normal cellular physiology, but an excess can result in cell injury. Iron in low-molecular-weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates; the result is wide-ranging impairment in cellular function and integrity. The rate of free radical production must overwhelm the cytoprotective defenses of cells before injury occurs. There is substantial evidence that iron overload in experimental animals can result in oxidative damage to lipids in vivo, once the concentration of iron exceeds a threshold level. In the liver, this lipid peroxidation is associated with impairment of membrane-dependent functions of mitochondria and lysosomes. Iron overload impairs hepatic mitochondrial respiration primarily through a decrease in cytochrome C oxidase activity, and hepatocellular calcium homeostasis may be compromised through damage to mitochondrial and microsomal calcium sequestration. DNA has also been reported to be a target of iron-induced damage, and this may have consequences in regard to malignant transformation. Mitochondrial respiratory enzymes and plasma membrane enzymes such as sodium-potassium-adenosine triphosphatase (Na(+) + K(+)-ATPase) may be key targets of damage by non-transferrin-bound iron in cardiac myocytes. Levels of some antioxidants are decreased during iron overload, a finding suggestive of ongoing oxidative stress. Reduced cellular levels of ATP, lysosomal fragility, impaired cellular calcium homeostasis, and damage to DNA all may contribute to cellular injury in iron overload. Evidence is accumulating that free-radical production is increased in patients with iron overload. Iron-loaded patients have elevated plasma levels of thiobarbituric acid reactants and increased hepatic levels of aldehyde-protein adducts, indicating lipid peroxidation. Hepatic DNA of iron-loaded patients shows evidence of damage, including mutations of the tumor suppressor gene p53. Although phlebotomy therapy is effective in removing excess iron in hereditary hemochromatosis, chelation therapy is required in the treatment of many patients who have combined secondary and transfusional iron overload due to disorders in erythropoiesis. In patients with beta-thalassemia who undergo regular transfusions, deferoxamine treatment has been shown to be effective in preventing iron-induced tissue injury and in prolonging life expectancy. The use of the oral chelator deferiprone remains controversial, and work is continuing on the development of new orally effective iron chelators.
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PMID:Iron toxicity and chelation therapy. 1241 32

Giant adrenal myelolipoma is an uncommon entity. We present the atypical MR imaging findings of a giant adrenal myelolipoma in a patient with homozygous beta-thalassemia with histopathology correlation. The tumor showed a drop in signal on the opposed-phase images, with no evidence of macroscopic fat contents, and demonstrated very high signal intensity on T2-weighted images. Giant adrenal myelolipoma should be considered in the differential diagnosis of tumors with the combination of the above MR imaging characteristics.
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PMID:Giant adrenal myelolipoma with minimal fat content in a patient with homozygous beta-thalassemia: appearance on MRI. 1457 4

Allogeneic hematopoietic cell transplantation (HCT) has been successfully used as replacement therapy for patients with aplastic anemia and hemoglobinopathies. Both autologous and allogeneic HCT following high-dose chemotherapy can correct manifestations of autoimmune diseases. The impressive allogeneic graft-versus-tumor effects seen in patients given HCT for hematological malignancies have stimulated trials of allogeneic immunotherapy in patients with otherwise refractory metastatic solid tumors. This session will update the status of HCT in the treatment of benign hematological diseases and solid tumors. In Section I, Dr. Rainer Storb reviews the development of nonmyeloablative conditioning for patients with severe aplastic anemia who have HLA-matched family members. He also describes the results in patients with aplastic anemia given HCT from unrelated donors after failure of responding to immunosuppressive therapy. The importance of leuko-poor and in vitro irradiated blood product transfusions for avoiding graft rejection will be discussed. In Section II, Dr. Guido Lucarelli reviews the status of marrow transplantation for thalassemia major and updates results obtained in children with class I and class II severity of thalassemia. He also describes results of new protocols for class III patients and efforts to extend HCT to thalassemic patients without HLA-matched family members. In Section III, Dr. Peter McSweeney reviews the current status of HCT for severe autoimmune diseases. He summarizes the results of autologous HCT for systemic sclerosis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, and reviews the status of planned Phase III studies for autologous HCT for these diseases in North America and Europe. He also discusses a possible role of allogeneic HCT in the treatment of these diseases. In Section IV, Dr. Richard Childs discusses the development and application of nonmyeloablative HCT as allogeneic immunotherapy for treatment-refractory solid tumors. He reviews the results of pilot clinical trials demonstrating graft-versus-solid tumor effects in a variety of metastatic cancers and describes efforts to characterize the immune cell populations mediating these effects, as well as newer methods to target the donor immune system to the tumor.
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PMID:Hematopoietic cell transplantation for benign hematological disorders and solid tumors. 1463 91

During the past 50 years, the role of allogeneic hematopoietic cell transplantation (HCT) has changed from a desperate therapeutic maneuver plagued by apparently insurmountable complications to a curative treatment modality for thousands of patients with hematologic diseases. Now, cure rates following human leukocyte antigen (HLA) allogeneic HCT with matched siblings exceed 85% for some otherwise lethal diseases, such as chronic myeloid leukemia, aplastic anemia, or thalassemia. In addition, the recent development of non-myeloablative conditioning and stem cell transplantation has opened the way to include elderly patients with a wide variety of hematologic malignancies. Further progress in adoptive transfer of T cell populations with relative tumor specificity would make the transplant procedure more effective and would extend the use of allogeneic HCT for treatment of non-hematopoietic malignancies.
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PMID:Hematopoietic cell transplantation: five decades of progress. 1473 93

Abnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired alpha-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired alpha-thalassemia are now recognized: acquired deletion of the alpha-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic down-regulation of alpha-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of alpha-thalassemia arising in a clonal myeloid disorder, and we discuss howATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms.
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PMID:Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. 1535 26

Extramedullary hematopoiesis often occurs in hemoglobinopathies, hemolytic anemias, leukemias, lymphomas, and myeloproliferative disorders. Liver, spleen, and lymph nodes are frequently involved. However, extramedullary hematopoiesis may also develop in other sites such as thymus, kidney, retroperitoneum, and paravertebral areas of the thorax. Extramedullary hematopoietic masses are often microscopic and asymptomatic, but sometimes they lead to tumor-like masses. We describe massive intrathoracic extramedullary hematopoiesis in a 41-year-old man with compound heterozygosis for beta-thalassemia and sickle cell anemia and functional asplenia. We also describe a 39-year-old man with beta-thalassemia intermedia, who was initially diagnosed as having tumor masses, but was later proved, by magnetic resonance imaging, to have extramedullary erythropoietic tissue. These observations provide further support to include extramedullary hematopoiesis among the differential diagnosis of tumor-like masses in patients with hematologic diseases.
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PMID:Intrathoracic masses due to extramedullary hematopoiesis. 1554 49

Autologous hematopoietic cells have been used as targets of gene transfer, with applications in inherited disorders, cell therapy, and acquired immunodeficiency. The types of cells include hematopoietic progenitor cells, lymphocytes, and mesenchymal stem cells. The inherited disorders thus far approached in clinical trials include severe combined immunodeficiency, common variable gamma-chain immunodeficiency, chronic granulomatous disease, and Gaucher disease. Preclinical studies are vigorously under way in thalassemia, sickle cell anemia, Wiskott-Aldrich syndrome and Fanconi anemia. Clinical trials of immunological therapy with gene-modified lymphocytes are under study in the treatment of malignancies. Clinical trials using anti-viral strategies for HIV infection in combination with autologous transplantation have begun, with additional approaches being developed. Gene therapy vectors are being developed to eliminate tumor cells contaminating autologous stem cell products. However, the risk of insertional mutagenesis and the potential for development of leukemia was highlighted by the first gene therapy trials in inherited immunodeficiency syndromes that achieved a therapeutic effect. Despite the slow progress of the field to date, there is extraordinary promise for gene therapy in the future.
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PMID:The current status of gene therapy in autologous transplantation. 1626 58


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