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)

The non-immune, non-spherocytic anemias result from multiple potential etiologies. We report a 16-year-old girl, who was presented with a long-standing anemia and normal blood screening tests except an elevated hemoglobin F. Her diagnosis of unstable hemoglobinopathy was made only after gene sequencing of the beta-globin chain.
Pediatr Blood Cancer 2005 Mar
PMID:A young girl with hemolytic anemia and elevated hemoglobin F. 1548 51

Although the first studies using DNA demethylating agents at low doses in hematologic neoplasia and hemoglobinopathies were initiated more than 20 years ago, development of this type of nonintensive treatment has only been spurred in the last 6 to 8 years by the discovery of many genes that are specifically hypermethylated in cancer. These provide a powerful rationale for using azanucleosides (and other small molecules being developed for DNA demethylation) as a novel means of pharmacologic targeting of cancer cells that is distinct from low-dose chemotherapy. Encouraging response rates of about 50% in myelodysplasia with 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine or DAC) have resulted in a number of phase III studies being initiated in this disorder. The development of such drugs for the treatment of acute myeloid leukemia (AML) is ongoing. While the specificity of DNA demethylation has been delineated by studying distinct genes or sets of genes, and proof-of-principle studies of in vivo methylation report demethylation and reactivation of genes like p15/INK4b and gamma-globin, responses to demethylating agents may be more complex. Specifically, so-called cancer testis antigens (CTAs) are intriguing targets for demethylation, since they are silenced in many hematopoietic disorders and may be reactivated by epigenetic therapy. Thus, demethylating agents and histone deacetylase inhibitors may also induce a T-cell-mediated antileukemic or antitumor effect.
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PMID:Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents. 1621 92

4-Phenylbutyrate (4-PBA) is an oral butyrate derivative that has recently been approved for treatment of urea cycle disorders and is under investigation in clinical trials of cancer, hemoglobinopathies, and cystic fibrosis (CF). We hypothesized that proteome profiling of IB3-1 cystic fibrosis bronchial epithelial cells treated with 4-PBA would identify butyrate-responsive cellular chaperones, protein processing enzymes, and cell trafficking molecules associated with the amelioration of the chloride transport defect in these cells. Protein profiles were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Over a pI range of 4-7 and molecular weight from 20 to 150 kDa a total of 85 differentially expressed proteins were detected. Most of the identified proteins were chaperones, catalytic enzymes, and proteins comprising structural elements, cellular defense, protein biosynthesis, trafficking activity, and ion transport. Subsets of these proteins were confirmed by immunoblot analysis. These data represent a first-draft of the pharmacoproteomics map of 4-PBA treated cystic fibrosis bronchial epithelial cells.
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PMID:Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cells. 1651 71

Renal medullary carcinoma is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, mainly sickle cell trait (SCT). Most patients present with metastatic disease and have a worse prognosis. An African-American male with sickle cell disease (HbSCD) who was diagnosed to have renal medullary carcinoma is presented here. The clinical, histologic and radiologic features of this tumor are described. In the setting of advanced disease, treatment modalities have proved largely unsuccessful. Given the shared demographic, clinical and radiographic features of these patients, awareness and early diagnosis may prove essential in improving survival.
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PMID:Renal medullary carcinoma. 1689 89

Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment modality for a number of hematologic malignancies, as well as inherited immunodeficiencies and hemoglobinopathies, and may also have a role in selected acquired autoimmune disorders. The complete or near-complete ablation of host immunity and subsequent establishment of donor-derived immunity that is required for successful engraftment and long-term outcomes provide a major obstacle to such transplantation approaches. A delicate balance exists between the need for the reconstituted donor-derived immunity to provide both protection against pathogenic challenges and graft-versus-malignancy activity, and the potentially harmful expansion of alloreactive T-cell clones mediating GvHD. The search for interventions that would allow more rapid and selective reconstitution of beneficial immune specificities continues to be informed by the development of new tools enabling a more precise dissection of the kinetics of reconstituting populations. This review summarizes more recent data on immune reconstitution following allogeneic transplantation in humans.
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PMID:Reconstitution of adaptive and innate immunity following allogeneic hematopoietic stem cell transplantation in humans. 1705 Feb 47

Anemia is a frequent complication of chronic kidney disease (CKD). Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells (RBCs). Anemia of CKD develops early and worsens with progressive renal insufficiency. Although over 40% of patients with CKD are anemic, anemia in this population is under-recognized and undertreated. Of considerable importance, anemia is a risk factor for cardiovascular disease and is associated with higher rates of hospitalization and mortality. Despite the availability of erythropoiesis-stimulating proteins (ESPs) to stimulate RBC production in CKD patients, approximately three fourths of patients initiating dialysis have a hemoglobin <11 g/dL. The recognition of anemia of CKD begins with an estimation of glomerular filtration rate (GFR), which can be far lower than a normal serum creatinine might suggest, especially in the elderly and in those with poor nutrition and muscle mass. If GFR is <60 mL/min/1.73 m(2), hemoglobin should be checked. The anemia is diagnosed when the hemoglobin is <12 g/dL in a man or a postmenopausal woman, or <11 g/dL in a premenopausal woman. The cause of anemia should be investigated in these individuals; this can range from erythropoietin deficiency due to CKD, to deficiency of vitamin B(12) and/or folate, iron deficiency, blood loss, inflammation, malignancy, and aluminum intoxication. After other causes of anemia have been excluded, CKD is the most likely etiology, and it should be treated with an ESP. Currently, epoetin alfa and darbepoetin alfa are the only 2 ESPs approved for use in the United States. Extended dosing of ESP has potential advantages for the patient and may also improve resource utilization. Consequently, both agents have been tested for dosing at extended intervals. Adequate iron stores--defined as transferrin saturation >20% and ferritin >100 mg--as well as ESP administration are needed to produce an appropriate increase in hemoglobin. Poor response to treatment with ESP can be due to many factors, including presence of iron deficiency, inflammation, continued blood loss, and hemoglobinopathy.
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PMID:Practical approach to the diagnosis and treatment of anemia associated with CKD in elderly. 1709 34

Renal medullary carcinoma (RMC) is an aggressive neoplasm occurring almost exclusively in adolescents and young adults with sickle cell (SC) hemoglobinopathies, usually sickle cell trait (SCT) or hemoglobin SC disease. The most common presentations are hematuria and flank or abdominal pain. It is a highly malignant tumor, and responses to chemotherapy are rare and transient resulting in a dismal prognosis. A high level of suspicion is necessary when evaluating at risk patients presenting with hematuria or flank pain, as currently it appears that only early diagnosis could potentially alter the outcome of this disease. We report a case of RMC in a young male patient with SCT, who presented to the emergency department with low back pain and microscopic hematuria, clinically mimicking acute obstructing urolithiasis. Our case emphasizes the need to consider alternate diagnoses when evaluating computed tomography scans for acute flank pain.
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PMID:Renal medullary carcinoma: unsuspected diagnosis at stone protocol CT. 1740 14

Busulfan is an alkylating agent used in a conditioning regimen prior to bone marrow transplantation. Busulfan has a narrow therapeutic index, giving rise to major liver toxicity (veno-occlusive disease), and a wide interpatient and intrapatient pharmacokinetic variability. This report presents the results of a population pharmacokinetic analysis leading to models based on underlying diseases requiring bone marrow transplantation. One hundred children received oral busulfan-based conditioning regimens between March 1998 and February 2006. Busulfan pharmacokinetic parameter estimates (Ka, first order absorption rate constant; Vs, volume of distribution related to the body weight; and Cl/F, apparent clearance) were estimated by using the nonparametric adaptative grid (NPAG) algorithm in patients divided into four groups according to initial diagnosis: metabolic diseases, hemoglobinopathies, hematological malignancies, and immune deficiencies. Ka and Vs did no differ significantly in the four subgroups. Cl/F and areas under the plasma concentration curve were significantly different in the four groups. Cl/F was significantly higher in the hemoglobinopathies group (P = 0.002), with a mean value of 7.78 L . h, whereas the immune deficiencies group was characterized by the lowest Cl/F (3.59 L . h). Interindividual variability was shown by high interindividual parameter percent coefficients of variation (CV%) but, nevertheless, with less diversity in the population parameter distributions for Vs in the three subgroups-metabolic diseases, hemoglobinopathies, and malignant diseases-and in Cl/F for patients with hemoglobinopathies. The fit was good for busulfan concentration predictions based on Bayesian individual posterior values, with little bias and good precision. In comparison with the overall population, the only model of subgroup presenting a greater precision was patients with hemoglobinopathies (P = 0.002). Use of these more specific models of a given disease may well result in more accurate individualization of busulfan dose regimens, especially in very sparse blood sampling situations.
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PMID:Influence of underlying disease on busulfan disposition in pediatric bone marrow transplant recipients: a nonparametric population pharmacokinetic study. 1741 71

Chronic cutaneous ulcers are commonplace in the developing world, especially in rural areas with poor living conditions and often result from the trauma of road-traffic injuries. Chronic cutaneous ulcers may also be due to vascular insufficiency, neuropathy, nodular leprosy, pressure, diabetes, or hemoglobinopathies, or they may be tropical ulcers. If poorly managed, these lesions may undergo malignant transformation. We evaluated the clinical histories and treatment outcomes of patients seen at the University of Calabar Teaching Hospital, between January 2000 and December 2004, who had histologic diagnosis of Marjolin's ulcer, in an attempt to identify risk factors for this problem. The six patients were men, age 30-70 years (mean, 42 years). Trauma was the leading cause of injury leading to ulceration: road-traffic accidents (four patients, 66.7%), fall (one patient, 16.7%), and flame burn (one patient, 16.7%). Most injuries involved the limbs: lower (four patients, 66.7%) and upper (one patient, 16.7%). The histologic diagnosis in all the cases were squamous cell carcinoma and mean latency period from injury to diagnosis of malignancy was 18.5 years. All the patients had been admitted because of poor results from topical treatment. Three patients (50%) were managed with wide excision and skin grafting with the lesions healed. Ignorance as well as economic and sociocultural factors were the underlying issues. Education concerning the risks associated with chronic wounds and the need for prompt and proper surgical management are recommended.
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PMID:Marjolin's ulcer: the importance of surgical management of chronic cutaneous ulcers. 1795 27

This article summarizes the progress of hematology in the recent tens years to show that experimental hematology used to pick up the 'hints' from clinical problems as the renewal of research directions and targets in experimental studies continuously. As the feedback, the results from lab investigations inserted into clinical practice and eventually made a quick modernization of hematology, which was actually a good model for the "translational research". The past few decades have witnessed tremendous advances in our understanding of normal hematopoiesis where genes dictate, epigenetics regulate, transcription factors mediate, and stem cells self-renew and differentiate. Dissection of disease pathogenesis not only elucidates molecular basis of disorders including hemoglobinopathy, aplastic anemia, hemophilia, hematopoietic malignancies such as leukemia and myeloproliferative disorders, but also provides therapeutic targets for drug development. Introduction of targeted therapies and combinatory targeting therapies greatly benefits hundreds of thousands of patients, and even turns acute promyelocytic leukemia from highly fatal to highly curable. In the 21st century the experimental hematology is entering the era of genomics and system biomedicine, and the pace of progress extrapolates to a prediction of hematologic neoplasms control in this century.
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PMID:[Experimental hematology bridging the gap between laboratory and clinic: hope of hematology]. 1831 92


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