Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pure red cell aplasia is a selective aplasia of the marrow erythroid cells. Unlike aplastic anemia, the marrow has a normal cellularity and the patients generally have normal leukocyte and platelet blood counts. The congenital form of the disease occurs in the firlst 1 1/2 years of life and is often responsive to corticosteroids. The acquired form may be secondary to infections, drugs, chemicals, or hemolytic anemia (aplastic crisis). In these cases it is often acute and self-limited with cessation of the infection or drug ingestion. It may also be secondary to systemic lupus erythematosus, rheumatoid arthritis, acute severe renal failure, severe nutritional deficiency, or diverse neoplasms, and may remit with treatment of the primary condition. When a thymoma is present, it should be resected since a remission is produced in 29 per cent of these patients. The remaining patients have an acquired primary form of the disease that tends to be chronic and in some cases may have an immune pathogenesis. A cytotoxic immunoglobulin inhibitor of the marrow erythroid cells or erythropoietin has been described and these patients may respond to prednisone and/or to cytotoxic immunosuppressive drugs such as cyclophosphamide and 6-mercaptopurine. Pure red cell aplasia appears to be more common than the literature has revealed and has stimulated much investigation into an immune pathogenesis for marrow failure.
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PMID:Diagnosis and treatment of pure red cell aplasia. 78 16

A high negative correlation (coefficient similar to 0.9) between increased 59Fe absorption from a diagnostic 0.56 mg 59Fe2+ dose and the depletion of available storage iron was observed in menstruating and pregnant women, fullterm and premature infants, blood donors, patients with infections, inflammations, tumors, hepatic cirrhosis, gastric surgery, increased urogenital or gastrointestinal blood loss. The increased diagnostic 59Fe2+ absorption is a reliable and sensitive indicator of at least depleted iron stores or prelatent iron deficiency as caused by iron malnutrition or maldigestion, increased iron requirement in pregnancy, infancy, urogenital or gastrointestinal blood loss. Although the messenger system which signalyzes the depletion of iron stores to the iron absorbing enterocytes of the duodenal and jejunal mucosa is not yet known available storage iron seems to control intestinal iron absorption under normal and the great majority o pathological condition in humans. Anemia per se or high erythropoietin levels in blood do not influence iron absorption since patients with even severe erythroblastic hypoplasia, aplastic anemia and megaloblastic anemia due to vitamin B12 deficiency absorb iron according to their iron stores. An only mild hyperplasia of the erythropoietic system in the bone marrow does also not effect iron absorption which was still under the control of available storage iron in patients with hereditary spherocytosis, nonspherocytic congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency, acquired hemolytic anemia and vitamin B12 deficiency induced megaloblastic anemia..
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PMID:Intestinal iron absorption under the influence of available storage iron and erythroblastic hyperplasia. Comparative studies in children with hereditary spherocytosis, nonspherocytic enzymopenic hemolytic anemia, acquired hemolytic anemia, vitamin B12 deficiency induced megaloblastic anemia, erythroblastic hypoplasia and aplastic anemia. 113 Jan 21

In patients with idiopathic aplastic anaemia (n = 34) and Fanconi's anaemia (n = 8), sampled once or on several occasions, serum erythropoietin (Epo) increased with increasing severity of anaemia with apparently similar rates of increase in each group. However, after adjustment for Hb, log Epo values for the Fanconi's anaemics tended to be greater than those for the idiopathic aplastic anaemics (P < 0.01). Erythropoietin concentrations in serum samples from patients with Fanconi's and idiopathic aplastic anaemias tended to be greater than in samples from patients with anaemias from protein energy malnutrition, myelodysplasia and iron deficiency. The results suggest that there is no deficiency of erythropoietin in Fanconi's and idiopathic aplastic anaemias and that if exogenous erythropoietin is of any benefit it would need to be administered in doses large enough to induce a significant increase in log Epo. Results of the study illustrate the need to take account of the assumptions which underlie interpretation of the statistical analysis. Use of erythropoietin values in place of log Epo gives misleading conclusions demonstrable as invalid as the conditions for normality of distribution of the data and homogeneity of variances were not satisfied.
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PMID:Serum immunoreactive erythropoietin in patients with idiopathic aplastic and Fanconi's anaemias. 148 41

In a previous pharmacokinetic study in Alzheimer patients great inter-individual variation and low oral bioavailability of the cholinesterase inhibitor tacrine (tetrahydroaminoacridine, THA) were found. In the present investigation oral and rectal administration of tacrine were compared with the aim to find a route for improved bioavailability through diminished first-pass metabolism in the liver. Eight patients suffering from Alzheimer's dementia were given tacrine by oral (25 and 50 mg b.i.d.) and rectal (12.5 and 25 mg b.i.d.) routes for 1 week with 4-6 weeks washout in between. Drug hydroxylation capacity in the patients was determined using the debrisoquine test. Levels of tacrine in plasma and cerebrospinal fluid (CSF) were determined and the cognitive performance was examined by the Mini-Mental State Examination (MMSE) and the Alzheimer Deficit Assessment Scale (ADAS). Tacrine was well tolerated in all but one patient, a slow hydroxylator, who developed an aplastic anemia. MMSE and ADAS scores did not significantly change, except for word recall which was improved on tacrine when given by the rectal route. Pharmacokinetic analysis of the two administration routes revealed that the drug dose may be reduced by almost 50% when given rectally compared to orally. Concentrations of tacrine in the CSF were significantly lower and correlated linearly with the concentrations in plasma.
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PMID:Tacrine in Alzheimer's disease: pharmacokinetic and clinical comparison of oral and rectal administration. 786 48

An autopsy case of malnutrition with spinal tract degeneration confined to the bilateral posterior columns is reported. The patient had schizophrenia in adolescence, and suffered from aplastic anemia in late middle age. Subsequently, he took little food due to delusions for 18 months until his death. He had malnutrition resulting in severe hypoproteinemia. He developed gait disturbance, loss of deep tendon reflexes and paresthesia of limbs. Neuropathological examination disclosed tract degeneration confined to the bilateral spinal posterior columns, in addition to the findings of aplastic anemia and hypoxic encephalopathy in the cerebrum. The myelin and axons were severely affected throughout the spinal cord; status spongiosus with many fatty-laden macrophages was seen in these lesions. Neurons in the posterior column nuclei were intact, while the dorsal roots and their ganglia were moderately affected. The unusual distribution and extension of the degeneration of the bilateral posterior columns in the poor nutritional state is discussed.
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PMID:Spinal tract degeneration confined to the bilateral posterior columns in malnutrition: report of an autopsy. 860 40

By ways of HPLC and RIA, multiple laboratory parameters were determined simultaneously in 84 patients of iron--deficiency anemia (IDA) or chronic aplastic anemia (CAA) with Liver-Blood Deficiency Syndrome (LBDS) diagnosed by differentiation of TCM. The results showed that LBDS had some pathophysiological characteristics such as decreased function of sympathicus and adrenal medulla axis, increasing of L-EK, lower energy metabolism of erythrocyte, lower rate of body metabolism, sodium and water imbalance, and abnormalities in hemorrheology and erythrocyte deformability. It is suggested that the patients with LBDS are in a state of protective compensation in blood volume regulation.
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PMID:[Preliminary study on pathophysiological basis of liver-blood deficiency syndrome]. 1007 22

Zygomycosis are invasive mould infections, rarely diagnosed in hematologic patients. Most of the cases published are in patients with prolonged neutropenia, along with other risk factors such as the use of prior broad-spectrum antibiotics (including new antifungal agents, such as voriconazole), diabetes mellitus (with or without ketoacidosis), malnutrition, iron overload (with or without the use of deferoxamine). These infections have poor prognosis due to the involvement of vital anatomic structures and late diagnosis. Until recent years, the treatment was based on high doses of amphotericin B plus surgical debridement. Here we present two patients with hematologic diseases (one with leukemia, the second with aplastic anemia) with an impaired immune system and the diagnosis of zygomycosis. The survival of one of them was mainly due to early diagnosis and surgical debridement; unfortunately the second was misdiagnosed as an extensive ecchymosis due to thrombocytopenia and died with CNS involvement.
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PMID:Zygomycosis in two hematologic cases. 2256 61

Normal human stem cells rely on low levels of active telomerase to sustain their high replicative requirements. Deficiency in telomere maintenance mechanisms leads to the development of premature aging diseases, such as dyskeratosis congenita and aplastic anemia. Mutations in the unique "insertion in fingers domain" (IFD) in the human telomerase reverse transcriptase catalytic subunit (hTERT) have previously been identified and shown to be associated with dyskeratosis congenita and aplastic anemia. However, little is known about the molecular mechanisms impacted by these IFD mutations. We performed comparative functional analyses of disease-associated IFD variants at the molecular and cellular levels. We report that hTERT-P721R- and hTERT-R811C-expressing cells exhibited growth defects likely due to impaired TPP1-mediated recruitment of these variant enzymes to telomeres. We showed that activity and processivity of hTERT-T726M failed to be stimulated by TPP1-POT1 overexpression and that dGTP usage by this variant was less efficient compared with the wild-type enzyme. hTERT-P785L-expressing cells did not show growth defects, and this variant likely confers cell survival through increased DNA synthesis and robust activity stimulation by TPP1-POT1. Altogether, our data suggest that multiple mechanisms contribute to cell growth defects conferred by the IFD variants.
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PMID:Multiple Mechanisms Contribute to the Cell Growth Defects Imparted by Human Telomerase Insertion in Fingers Domain Mutations Associated with Premature Aging Diseases. 2688 40

Maintenance of the hematopoietic stem cell (HSC) compartment depends on the ability to metabolize exogenously and endogenously generated toxins, and to repair cellular damage caused by such toxins. Reactive aldehydes have been demonstrated to cause specific genotoxic injury, namely DNA interstrand cross-links. Aldehyde dehydrogenase 2 (ALDH2) is a member of a 19 isoenzyme ALDH family with different substrate specificities, subcellular localization, and patterns of expression. ALDH2 is localized in mitochondria and is essential for the metabolism of acetaldehyde, thereby placing it directly downstream of ethanol metabolism. Deficiency in ALDH2 expression and function are caused by a single nucleotide substitution and resulting amino acid change, called ALDH2*2. This genetic polymorphism affects 35-45% of East Asians (about ~560 million people), and causes the well-known Asian flushing syndrome, which results in disulfiram-like reactions after ethanol consumption. Recently, the ALDH2*2 genotype has been found to be associated with marrow failure, with both an increased risk of sporadic aplastic anemia and more rapid progression of Fanconi anemia. This review discusses the unexpected interrelationship between aldehydes, ALDH2 and hematopoietic stem cell biology, and in particular its relationship to Fanconi anemia.
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PMID:Aldehyde dehydrogenase 2 in aplastic anemia, Fanconi anemia and hematopoietic stem cells. 2765 66

Clinical copper deficiency is now more frequently recognized. Hematologically, it can present as anemia (microcytic, normocytic, or macrocytic) and neutropenia. Thrombocytopenia is relatively rare. Neurologically, it can manifest as myelopathy and peripheral neuropathy simulating subacute combined degeneration. Bone marrow findings can mimic myelodysplasia resulting in occasional inappropriate referral for bone marrow transplantation. Other conditions with similar presentations include infections, drug toxicity, autoimmunity, B12 deficiency, folate deficiency, myelodysplastic syndrome, aplastic anemia, and lymphoma with bone marrow involvement. Hematological, but not neurological, manifestations respond promptly to copper replacement, making early diagnosis essential for good outcome. Common risk factors for copper deficiency are foregut surgery, dietary deficiency, enteropathies with malabsorption, and prolonged intravenous nutrition (total parenteral nutrition). We present a unique case of copper deficiency, with no apparent known risk factors.
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PMID:Copper deficiency, a new triad: anemia, leucopenia, and myeloneuropathy. 2904 59


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