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)

A 22-year-old male with a history of hemoglobin E beta zero-thalassemia presented with thoracic spinal cord compression due to extramedullary hematopoietic tissue in the epidural space. Following decompressive laminectomy, this epidural mass was irradiated to 20.4 Gy in 12 fractions. The patient made a complete recovery from his neurological symptoms following treatment. Follow-up radiographs showed significant reductions in size of the extradural tumor. Results from this case supported by review of the literature suggest that radiation therapy, with or without decompressive surgery, is an effective therapy in treatment of patients with spinal cord compression due to epidural extramedullary hematopoietic tissue.
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PMID:Combined radiotherapeutic and surgical management of a spinal cord compression by extramedullary hematopoiesis in a patient with hemoglobin E beta-thalassemia. 809 37

Since the early descriptions of sickle cell anemia, it has been clear that genotype at a single locus rarely completely predicts phenotype. This paper reviews explanations for phenotypic variability in some monogenic diseases. In cystic fibrosis, there is strong correlation between genotype and pancreatic phenotype but only weak association with respiratory phenotype, possibly due to differential inheritance of alleles at loci controlling susceptibility to respiratory infection. In addition, disease mutations have been shown to have more or less severe effect, depending on other variation within the cystic fibrosis gene. In phenylketonuria, genotype at the phenylalanine hydroxylase locus appears to explain the biochemical phenotype, but not the intellectual status. There may be genetically determined variation in flux through the minor metabolic pathways for phenylalanine, influencing levels of alternative metabolites involved in mental development. Phenotypic discordance in sickle cell anemia and beta-thalassemia has been associated with the co-inheritance of genes for hereditary persistence of fetal hemoglobin. A mouse locus has been identified that influences tumour number in mice with the multiple intestinal neoplasia gene. Understanding of the genetic interactions that determine phenotype in apparently monogenic diseases should lead to clarification of the role of different genes in polygenic diseases with complex inheritance patterns, as well as enhancing the ability to predict the outcome of a disease mutation.
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PMID:Relationship between genotype and phenotype in monogenic diseases: relevance to polygenic diseases. 872 77

The epidemiological characteristics of 359 difficult intubations resulted from retrospectively collected data in a series of 4.742 individual anaesthetic case records of consecutive adult patients (2392 men, 2350 women) undergoing general anaesthesia for routine surgery. The preoperative assessment of each patient's airway was performed using standardized guidelines. Mandibular length, body weight and mobility of jaw, head and neck were evaluated with simple measurements. The presence of protruding maxilla or upper teeth, tongue tumor or cyst, long narrow mouth, short muscular neck and deviation of larynx or trachea was based on clinical and/or radiological examination. Severity of difficulty in intubation was estimated on a five-point scale grades (0-4) according to the view obtained at laryngoscopy and the final outcome of airway management. Difficult intubation (grades 1-4) was confirmed in 359 cases (7.6%) of which 208 were anticipated (57.2%). The effectiveness of preoperative evaluation had a positive correlation with the level of difficulty since, the greater the grade of difficulty the greater the sensitivity. The prevalence of failed intubation (grade 4) was 0.5%. Risk factors which had been correlated with the relative size of the tongue proved to have low probability and level of difficulty of intubation. The most important risk factor was limited jaw movement (median grade of difficulty: 4, positive predictive value: 75.0%). Large endemic goitre and thalassaemia constitute RFs contributing occasionally to difficult airway. The positive predictive value was 61.5% and 40.9% respectively. The combination of risk-factors had a cumulative impact contributing to the high level of difficulty.
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PMID:Evaluating the difficult airway. An epidemiological study. 891 85

Extramedullary hematopoiesis is a common accompaniment of a variety of hematologic diseases such as hereditary spherocytosis, thalassemia and myelofibrosis. The association of extramedullary hematopoiesis with polycythemia vera in the proliferative phase is much less usual. We report a patient who presented with paraplegia due to spinal cord compression; clinical investigation revealed a paravertebral hematopoietic tumor, and the diagnosis of polycythemia vera was then established.
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PMID:Spinal cord compression due to extramedullary hematopoiesis in the proliferative phase of polycythemia vera. 892 92

The cytosine analog 5-aza-2'-deoxycytidine has been used clinically to reactivate genes silenced by DNA methylation. In particular, patients with beta-thalassemia show fetal globin expression after administration of this hypomethylating drug. In addition, silencing of tumor suppressor gene expression by aberrant DNA methylation in tumor cells may potentially be reversed by a similar regimen. Consistent with its function in maintaining tumor suppressor gene expression, 5-aza-2'-deoxycytidine significantly reduces intestinal tumor multiplicity in the predisposed Min mouse strain. Despite its utility as an anti-cancer agent, the drug is highly mutagenic by an unknown mechanism. To gain insight into how 5-aza-2'-deoxycytidine induces mutations in vivo, we examined the mutational spectrum in an Escherichia coli lac I transgene in colonic DNA from 5-aza-2'-deoxycytidine-treated mice. Mutations induced by 5-aza-2'-deoxycytidine were predominantly at CpG dinucleotides, which implicates DNA methyltransferase in the mutagenic mechanism. C:G-->G:C transversions were the predominant class of mutations observed. We suggest a model for how the mammalian DNA methyltransferase may be involved in facilitating these mutations. The observation that 5-aza-2'-deoxycytidine-induced mutations are mediated by the enzyme suggests that novel inhibitors of DNA methyltransferase, which can inactivate the enzyme before its interaction with DNA, are needed for chemoprevention or long term therapy.
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PMID:Mutagenicity of 5-aza-2'-deoxycytidine is mediated by the mammalian DNA methyltransferase. 911 51

A search of the Human Genome Sciences database of expressed sequence-tagged DNA fragments, for sequences containing homology to known yeast DNA recombination and repair genes, yielded a cDNA fragment with high homology to RAD54. Here we describe the complete cDNA sequence and the characterization of the genomic locus coding for the human homologue of the yeast RAD54 gene (hRAD54). The yeast RAD54 belongs to the RAD52 epistasis group and appears to be involved in both DNA recombination and repair. The hRAD54 gene maps to chromosome 1p32 in a region of frequent loss of heterozygosity in breast tumors and encodes a protein of M(r) 93,000 that displays 52% identity to the yeast RAD54 protein. The hRAD54 protein sequence additionally contains all seven of the consensus segments of a superfamily of proteins with presumed or proven DNA helicase activity. Mutations in genes with consensus helicase homology have been found in cancer-prone syndromes such as xeroderma pigmentosum and Bloom syndrome as well as Werner's syndrome, in which patients age prematurely, and the X-linked mental retardation with alpha-thalassemia syndrome, ATR-X. We have examined the hRAD54 gene in several breast tumors and breast tumor cell lines and, although the gene region appears to be deleted in several tumors, at present we have found no coding sequence mutations.
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PMID:Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. 919 13

The purpose of this study was to characterize the effects of sodium 4-phenylbutyrate (phenylbutyrate) on the proliferation, morphology, migration and invasiveness of malignant glioma cells in vitro. Phenylbutyrate is a novel differentiating and cytotoxic compound used clinically with low toxicity in the treatment of beta-thalassemia, sickle cell anemia and urea cycle disorders. Preliminary clinical trials testing phenylbutyrate as an anti-cancer agent have included patients with malignant glioma. However, little information is available regarding the effects of phenylbutyrate on glioma cells, particularly with respect to the expression of genes important in the pathogenesis of glial malignancy. In experiments reported here, glioma cell lines and explant cells from a tumor patient were exposed to 2, 4 and 8 mM phenylbutyrate and compared to untreated control cells. The effect on cellular proliferation was assessed using cell counts and DNA flow cytometry. Changes in morphology were evaluated using vimentin staining. Scratch and Matrigel assays were performed to assess changes in cellular migration and invasiveness. Finally, Northern blot analysis was used to study c-myc and urokinase expression. Phenylbutyrate was found to have dose-dependent inhibitory effects on glioma cell proliferation, morphology, migration, invasiveness and c-myc and urokinase expression. Mean growth-inhibitory (IC50) phenylbutyrate concentrations ranged from 0.5 mM for T98G cells to 5.0 mM for explant cells. Phenylbutyrate treatment reduced % S phase cells, increased % G0/G1 cells, and produced morphologic changes consistent with induction of differentiation. 24 hours of treatment with 4 mM phenylbutyrate resulted in a 50% reduction in migration and invasiveness. Northern blots showed a decrease in urokinase and c-myc expression at non-cytotoxic doses. We conclude that phenylbutyrate is a promising candidate compound for treating patients with malignant glioma.
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PMID:Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration and invasiveness of malignant glioma cells. 952 87

We report a case of adrenal extramedullary hematopoiesis in a 27-year-old woman with beta-thalassemia. She underwent cholecystectomy for gallstones and splenectomy for splenomegaly at the age of 20 years. In January 1996, she was admitted to our hospital because of a palpable nontender mass in the right subcostal area. Ultrasound, computed tomography, and magnetic resonance imaging disclosed a right suprarenal mass 7.5 x 5.8 cm in size. Surgical exploration and biopsy confirmed the diagnosis of extramedullary hematopoietic (EMH) tumor. The tumor was left in situ. Subsequent follow-up showed no increase in the size of the tumor and no progression of anemia. The patient remained asymptomatic, and no additional EMH tumor developed. Surgery or radiotherapy should be performed only when EMH tumors cause symptoms, such as during spinal cord compression. Adrenal EMH tumors should be considered in thalassemia patients with an adrenal mass, to avoid unnecessary surgical procedures.
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PMID:Adrenal extramedullary hematopoietic tumor in a patient with beta-thalassemia. 965 Apr 75

We experienced with a case showing a mediastinal mass on chest X-ray accompanied by thalassemia. Preoperative diagnosis for this mass was a neulogenic tumor based on the findings of roentgenogram. Surgical resection of the mass was performed, and histology revealed that it was a mass-like tissue presenting extramedullary hematopoiesis. Generally speaking, any tissues functioning as extramedullary hematopoiesis should not be resected in patients with anemia or showing bone marrow suppression. And it is also said that 111In-chloride scintigram is highly diagnostic for patients with a tissue functioning as extramedullary hematopoiesis. We had not performed 111In-chloride scintigram for this case preoperatively and performed a resection of the mediastinal mass carelessly. Care should be taken not to perform surgical resection carelessly in cases with a mediastinal mass accompanied by anemia or bone marrow suppression.
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PMID:[A case of surgically resected mediastinal mass histologically proven to be a mass-like tissue presenting extramedullary hematopoiesis accompanied by thalassemia]. 974 9

The authors report a case of beta-thalassemia/hemoglobin E disease with extramedullary haematopoietic tumor which developed at the small intestine and caused intussusception. A 7 year-old boy with homozygous beta-thalassemia/hemoglobin E presented with recurrent abdominal pain. The abdominal ultrasonography showed ileo-ileal intussusception with a solid mass as the leading point. Resection of the ileal segment was performed. Pathological examination revealed an extramedullary haematopoietic tumor forming an intraluminal polypoid mass, being the leading point of the intussusception. Extramedullary haematopoiesis in the intestinal tract is rare. To our knowledge, this is the first case of extramedullary haematopoietic tumor that produced intussusception of the small intestine in a beta-thalassemia/hemoglobin E patient.
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PMID:Extramedullary haematopoietic tumor producing small intestinal intussusception in a beta-thalassemia/hemoglobin E Thai boy: a case report. 1086 1


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